Cancer Biomarkers - Volume Pre-press, issue Pre-press

Authors: Shahbazi, Shirin | Khorasani, Maryam | Mahdian, Reza

Article Type: Research Article

Abstract: OBJECTIVES: The ectopic expression of coagulation Factor VII has been shown in various cancers. Recently, F7 gene has been identified as a direct target of the androgen receptor in breast cancer. In this study, we examined the mRNA expression of F7 and AR in clinical sample series of prostate cancer and BPH. MATERIAL AND METHODS: All the prostate cancer patients were new cases with no medical history of surgery or chemotherapy. The tissue samples were assigned as either prostate cancer tumor (n= 45) harboring at least 80% tumor cell content, or BPH (n= 36). Relative …AR and F7 mRNA expression in each tissue sample was normalized to the mean of the Ct values determined for GAPDH and PSA genes. RESULTS: Mean plasma level of prostate specific antigen (PSA) was 17.82 ± 3.71 ng/ml and 7.71 ± 1.28 ng/ml (Mean ± SEM) in PCa and BPH group, respectively. AR mean expression was up-regulated 22.468 fold in clinical tumor sample cohort (S.E., 0.175-2,916, 95% CI: 0.001-126,764, P= 0.001). The mean expression of F7 gene in tumor tissues relative to PBH samples was 6.981 (S.E., 0.099-413.001, 95% CI: 0.002-34,183, P= 0.012). ANOVA analysis of the gene expression results showed significant correlation between F7 and AR mRNA expression in tumor samples (p< 0.001). CONCLUSIONS: Our study findings suggest a link between FVII and AR in prostate cancer pathogenesis. F7 gene expression could be up regulated via various AR mediators affecting the promoter region of the F7 gene. Should this be confirmed by further studies, it may be suggested as a potential contributing factor in prostate cancer. Show more

Keywords: Prostate cancer, FVII, F7 gene, androgen receptor, AR gene, gene expression

DOI: 10.3233/CBM-160647

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-6, 2016

Authors: Wu, Zhengrong | Zhou, Liangjing | Ding, Guoping | Cao, Liping

Article Type: Research Article

Abstract: BACKGROUND: The miR-212 was among the top differentially expressed miRNAs in pancreatic ductal adenocarcinoma (PDAC). OBJECTIVE: The aim of this study was to investigate the expression of miR-212 in PDAC and evaluate its correlation with major clinicopathologic features and patients' survival. METHODS: Fluorescence in situ hybridization (FISH) was adopted to examine miRNA expression in 45 pancreatic cancer and 20 normal pancreatic tissues. The relationship of miR-212 expression with clinicopathologic parameters and clinical outcome was evaluated. RESULTS: miR-212 was confirmed to have significantly higher expression in PDAC compared with normal …pancreatic tissues (51.1% vs 10%, p< 0.01). High expression of miR-212 was significantly associated with tumor size (p = 0.048) and tumor stage (p = 0.023). Moreover, in univariant analysis, patients with high expression of miR-212 demonstrate significantly poorer overall survival (p= 0.02). CONCLUSIONS: High expression of miR-212 in PDAC is associated with shorter overall survival. It may be not only a potential prognostic marker, but also a possible therapeutic target in PDAC. Show more

Keywords: microRNA-212, Pancreatic neoplasms, Prognosis

DOI: 10.3233/CBM-160671

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-5, 2016

Authors: Tusong, Hamulati | Maolakuerban, Naibijiang | Guan, Jin | Rexiati, Mulati | Wang, Wen-Guang | Azhati, Baihetiya | Nuerrula, Yiliyaer | Wang, Yu-Jie

Article Type: Research Article

Abstract: OBJECTIVE: microRNAs (miRNAs) plays an important role in tumor development and progression and act as oncogenes or tumor suppressor genes in the carcinogenesis process. miRNA is stable in serum, and recent studies have demonstrated the feasibility of using circulating miRNA as biomarkers in cancer patients. However, currently, no serum biomarkers for the early diagnosis and prognosis of renal cell carcinoma (RCC) have been reported. Therefore, a new molecular marker for early diagnosis and evaluation of recurrence after surgery is required. Our purpose was to identify miRNA signatures that could distinguish the serum of RCC patients from matched healthy controls …and validate identified miRNAs as potential biomarkers for RCC. METHOD: Serum samples from 30 RCC patients were collected before and 1 month after surgery. 30 cancer-free blood donor volunteers with no history of any cancer were recruited from the same institute. miR-21 and miR-106a expression levels were determined by real-time PCR. RESULT: The serum miR-21 level was significantly higher in RCC patients (median, 8.34) than in healthy control individuals (median, 0.70; p= 0.001). A month after surgery, serum miR-21 levels (median, 0.69) were significantly reduced (p= 0.032). The serum miR-106a level was higher in RCC patients (median, 8.99) compared with controls (median, 0.96; p= 0.000), while miR-106a levels (median, 1.01) were reduced a month after surgery (p= 0.028). The expression level of miR-21 and miR-106 a in RCC patients increased significantly, while miR-21 and miR-106a decreased after surgery. This outcome suggests that serum miR-21 and miR-106a expression level was closely related with kidney cancer tissue. CONCLUSION: We conclude that serum miR-21 and miR106a are expected to be molecular markers for RCC. Show more

Keywords: Renal cell carcinoma, microRNAs, serum biomarker, Hippel Lindau (VHL), phosphates and tensing homolog (PTEN)

DOI: 10.3233/CBM-160676

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-7, 2016

Authors: Du, Wenhan | Shen, Ting | Li, Hui | Liu, Yingying | He, Lagu | Tan, Li | Hu, Min

Article Type: Research Article

Abstract: OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) has been proved as a sensitive biomarker in acute and chronic renal injury. Renal impairment is a common complication of multiple myeloma (MM). We attempt to assess the value of NGAL for the early and accurate diagnosis of renal injury in MM patients. METHODOLOGY: Forty-five MM patients with CKD stage I to V(MM-renal group), 20 MM patients with normal kidney function (MM-non-renal group), and 37 healthy volunteers (healthy control) were compared for serum and urinary NGAL and other renal injury biomarkers (Creatinine[CRE]; Cystatin-C [CysC]; N-acetyl-beta-D-glucosaminidase [NAG]). Other biomarkers reflect the inflammation …and tumor burden like high-sensitivity C-reactive protein(hs-CRP) and urine free light chain were also detected. RESULTS: Among the biomarkers of renal injury, the assessment of serum CysC, CRE and NGAL was a reliable tool to distinguish MM-renal from MM-non-renal. Both serum and urinary NGAL levels were higher in MM-renal patients than in MM-non-renal or healthy controls (187.10 (45.60-699.60) vs 136.70 (47.70-216.50) vs 117.7 (69.3-192.3), P< 0.01; 37.50 (6.30-412.10) vs 18.00 (0.50-66.50) vs 11.2 (0.9-69.1), P< 0.01). Univariate analysis showed that both serum (Odds Ratio = 1.009; 95%CI 1.002-1.017; P= 0.018) and urinary NGAL (Odds Ratio = 1.038; 95%CI 1.003-1.073; P= 0.031) as well as serum CysC (Odds Ratio = 9.875; 95%CI 1.685-57.882; P= 0.011) were strong predictors for the risk of renal injury in MM patients. Moreover, the urinary NGAL level was negatively correlated with estimated glomerular filtration rate (eGFR) (r= -0.586, P= 0.00003) and has a tendency towards positive correlation with urine free light chain (r = 0.235, P = 0.124) and hs-CRP (r = 0.379, P = 0.074). CONCLUSIONS: The present study demonstrated that urinary NGAL was not superior to serum NGAL in distinguishing MM-renal group from MM-non-renal group. And it could be considered an independent predictor of renal injury from multiple myeloma reflecting active kidney damage, tumor burden, and inflammation. Show more

Keywords: Neutrophil gelatinase-associated lipocalin, multiple myeloma, renal impairment

DOI: 10.3233/CBM-160672

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-6, 2016

Authors: Rucksaken, Rucksak | Charoensuk, Lakhanawan | Pinlaor, Porntip | Pairojkul, Chawalit | Khuntikeo, Narong | Pinlaor, Somchai

Article Type: Research Article

Abstract: BACKGROUND: Cholangiocarcinoma (CCA), a malignant tumor of the biliary epithelium, is a tumor with an ineffective diagnosis and poor prognosis. We have previously identified an overexpression of orosomucoid 2 (ORM2) along with CCA development in hamsters using a proteomics technique. OBJECTIVE: To evaluate plasma ORM2 as a candidate risk biomarker for CCA in humans. METHODS: Overexpression of ORM2 in CCA patients was assessed by western blotting and immunohistochemistry. The diagnostic efficacy of ORM2 was investigated in the plasma of patients with hepatobiliary diseases - including 46 cholangitis patients and 70 CCA patients - …compared with 20 healthy individuals, using enzyme-linked immunosorbent assay (ELISA). RESULTS: Overexpression of ORM2 was observed in the cytoplasm of bile duct tumor cells and in the adjacent normal hepatocytes at a much higher intensity than in normal bile duct cells. Western blot analysis revealed that its expression was significantly higher in the plasma of CCA patients compared with that of healthy individuals (P < 0.01). ELISA showed that plasma ORM2 levels were significantly elevated in CCA and cholangitis groups compared with healthy individuals (P < 0.0001). The sensitivity and specificity of ORM2 in distinguishing CCA patients from healthy patients were 92.86% and 73.68%, respectively. CONCLUSIONS: Plasma ORM2 could serve as a new risk marker for CCA. Show more

Keywords: Biomarker, cholangiocarcinoma, cholangitis, hepatobiliary disease, orosomucoid 2, ELISA

DOI: 10.3233/CBM-160670

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-8, 2016

Authors: Yazici, Pinar | Demir, Uygar | Bozkurt, Emre | Isil, Gurhan R. | Mihmanli, Mehmet

Article Type: Research Article

Abstract: BACKGROUND: Although the red cell distribution width (RDW) has been reported as a reliable predictor of prognosis in several types of cancer, to our knowledge the prognostic value of RDW in gastric carcinoma has not been studied, so far. OBJECTIVE: We aimed to investigate the role of red cell distribution width (RDW) in predicting prognosis in gastric cancer patients. METHODS: All gastric cancer patients who underwent curative surgery (n= 172, 110M/62F) over a five-year study period were evaluated. Data on demographics, preoperative RDW levels, tumor characteristics (early stage: I and II, advanced stage: …IIIA-B-C), disease-free (DFS) and overall survival (OS) were retrospectively reviewed. Patients were classified as high RDW group (RDW ≥ 16, n= 62) or low RDW group (RDW < 16, n= 110). RESULTS: Overall mortality and postoperative 60-day mortality in both groups were 55% and 14%, respectively. A borderline significant association between RDW (0.063) and mortality was noted. Preoperative RDW levels were significantly higher in patients with short-term mortality (17.9 ± 4.3 vs. 16 ± 3.2, p= 0.015). In high RDW group, the incidence of advanced gastric cancer was significantly higher (75 vs. 51%, p= 0.002), whereas DFS (0.035) and OS (p= 0.04) were lower. CONCLUSION: The frequency of advanced cancer is high in patients with high RDWvalues. High RDW values were strongly associated with short-term mortality although only a borderline relationship with overall survival was observed. Show more

Keywords: Gastric cancer, red cell distribution width, staging, prognosis

DOI: 10.3233/CBM-160668

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-7, 2016

Authors: Xu, Lei | Zhou, Xin | Wang, Jian | Zhu, Wei | Liu, Ping

Article Type: Research Article

Abstract: BACKGROUND: Recently, many studies have investigated the value of the hematologic markers in the prognosis of gastric cancer (GC). However, most studies only focused on the pre-operative markers. The aim of this study was to investigate the prognostic value of the hematologic markers of resectable GC patients at three different periods of the treatment (preoperative, postoperative and before the first chemotherapy). METHODS: Clinical data from 451 GC patients were retrospectively collected. Hematologic markers including leukocyte, neutrophil, lymphocyte, red blood cell (RBC), platelet, mean platelet volume (MPV), neutrophil proportion (NP), lymphocyte proportion (LP), neutrophil lymphocyte ratio (NLR), …and platelet lymphocyte ratio (PLR) were adopted as potential prognostic biomarkers. The Kaplan-Meier method and Cox regression model were applied to reveal the prognostic significance of the hematologic markers. RESULTS: Preoperative PLR was independently associated with overall survival (OS) via multivariate analysis (hazard ratio, 1.399; 95% confidence interval, 1.015-1.928; p = 0.04). Elevated PLR predicted a larger tumor size (P< 0.001), deeper tumor invasion (P= 0.035) and elevated level of CEA (P= 0.012). CONCLUSIONS: Although only high preoperative PLR could serve as an independent unfavorable prognostic factor, other markers such as preoperative and postoperative NLR could also provide additionally prognostic information. Show more

Keywords: Hematological parameters, PLR, NLR, gastric cancer, prognosis

DOI: 10.3233/CBM-160648

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-9, 2016

Authors: Rahimi, Farzaneh | Karimi, Jamshid | Goodarzi, Mohammad Taghi | Saidijam, Massoud | Khodadadi, Iraj | Razavi, Amir Nader Emami | Nankali, Maryam

Article Type: Research Article

Abstract: BACKGROUND: Ovarian cancer is one of the important challenges in the field of gynecologic oncology because of some problems in understanding its etiology and pathogenesis. Receptor for advanced glycation end products (RAGE) is a multiligand trans-membranous receptor which is upregulated in some human cancers. Mechanisms of RAGE involvement in carcinogenesis of ovarian cancer are unknown. OBJECTIVE: This study aimed to investigate the expression of RAGE in ovarian cancers and its association with clinicopathological characteristics. METHODS: The RAGE expression level in ovarian cancer and corresponding noncancerous tissues were analyzed by real time quantitative RT-PCR …and immunohistochemistry techniques. RESULTS: Results indicated that RAGE gene was overexpressed in ovarian cancer tissue compared with adjacent noncancerous tissue (p < 0.001). A significant association between RAGE expression and tumor size (p = 0.04), depth of stromal invasion (p = 0.031), lymphovascular invasion (p = 0.041) and stage of cancer (p = 0.041) was observed. The receiver operating characteristic (ROC) analyses yielded the area under the curve (AUC) values of 0.86 for RAGE in discriminating ovarian cancer samples from non-cancer controls. CONCLUSIONS: In conclusion overexpression of RAGE in ovarian cancer may be a useful biomarker to predict tumor progression. Show more

Keywords: Carcinoma, ovarian cancer, receptor for advanced glycation end products, tumor

DOI: 10.3233/CBM-160674

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-8, 2016

Authors: Zhao, Qing | Cui, Zheng | Zheng, Yan | Li, Qun | Xu, Changyuan | Sheng, Xueqi | Tao, Mei | Xu, HuiXin

Article Type: Research Article

Abstract: BACKGROUND AND AIMS: Peroxisome proliferator-activated receptor-α (PPAR-α ) activation has been reported to reduce myocardial ischemia-reperfusion (I/R) injury by inhibiting cell apoptosis. However, the antiapoptotic mechanism of PPAR-α is still unknown. Fenofibrate is a PPAR-α agonist In the present study, we investigate the effects and relevant mechanism of fenofibrate on experimental myocardial ischemia-reperfusion (I/R) injury in rats. METHODS: Adult male Wistar rats were pretreated with fenofibrate (80 mg/kg) daily for a period of 7 days. After the treatment period, myocardial I/R injury model was made …by left anterior descending coronary artery ligation for 45 min and reperfusion for 120 min. Myocardial infarct size, malondialdehyde (MDA) cleaved-caspase-9 protein expression, PPARα and uncoupling protein 2 (UCP2) mRNA levels in myocardial tissue were detected Cell apoptosis was detected by Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Serum lactate dehydrogenase and creatine kinase activities were measured in rats pretreated with fenofibrate The ultrastructure of myocardial tissues was observed. RESULTS: Significant increases in myocardial cell apoptosis, malondialdehyde (MDA) level and cleaved-caspase-9 protein expression level in myocardial tissue were observed, along with reductions of PPARα and uncoupling protein 2 (UCP2) mRNA levels in myocardial tissue of the experimental myocardial ischemia-reperfusion (I/R) injury in rats. Impaired mitochondria were also observed under electron microscopic. However, pretreatment of ischemia/reperfusion rats with fenofibrate brought the biochemical parameters and related genes expression levels to near normalcy, indicating the protective effect of fenofibrate against myocardial ischemia/reperfusion injury in rats. CONCLUSIONS: The PPAR-α activator fenofibrate conferred cytoprotective effect against myocardial ischemia-reperfusion (I/R) injury in rats. Associated mechanisms involved decreased cleaved-caspase-9 expression and decreased cell apoptosis. Show more

Keywords: Acute myocardial ischemia/reperfusion injury, apoptosis, PPARα, caspase-9

DOI: 10.3233/CBM-170572

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-9, 2017

Authors: Zhang, Meifeng | Wu, Wei | Gao, Ming | Fei, Zhewei

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVE: To investigate the diagnostic potentials of microRNA-451(miR-451) in papillary thyroid carcinoma (PTC) diagnosis and lymph node (LN) metastasis, formalin-fixed, paraffin-embedded (FFPE) tissue specimens corresponding to PTC tumors (n = 60) and their normal counterparts (N ormal tissues A djacent to T umor, NAT, n = 60), along with sera from PTC patients with malignant tumors (n = 70) and benign lesions (n = 70) were analyzed for the expression of miR-451 by real-time PCR. …METHODS: The usefulness of miR-451 expression as a prognostic marker for diagnosis of PTC malignancies was evaluated by Receiver Operating Curve (ROC). We reported that when compared to those in NAT, the levels of miR-451 in FFPE tissues from various stages of PTC patients (n = 60) were significantly lower (Mean ± SEM; 12.62 ± 1.73 vs 38.8 ± 3.51, p < 0.0001). Receiver operating curve (ROC) analysis revealed that the a rea u nder c urve (AUC) was 0.808; suggesting miR-451 expression was a reliable tissue biomarker for PTC malignancies. Further in depth analyses of these specimens revealed that miR-451 levels were significantly lower in PTC patients with lymph node (LN) metastasis than those without LN metastasis (3.96 ± 1.67 vs. 14.15 ± 1.95, p = 0.006) with calculated AUC of 0.792, supporting the notion that miR-451 expression was also a good indicator for PTC lymph node involvements. Analyses sera from the cohorts of PTC patients indicated that miR-451 levels in patients with malignant lesions (n = 70) were significantly lower (10.72 ± 1.52 vs. 19.28 ± 2.73, p = 0.010) than those with benign ones (n = 70). Parallel analyses of serum miR-451 levels in patients with LN metastasis also showed that they were significantly lower when compared to those without LN metastasis (6.79 ± 2.29 vs. 12.08 ± 1.86, p = 0.017). RESULTS: ROC analyses revealed that AUC was 0.626 for malignancies and was 0.690 for lymph node involvement, respectively, suggesting that miR-451was a modest blood based biomarker for PTC malignancies and lymph node metastasis. CONCLUSIONS: We concluded that miR-451 expression is a reliable FFPE tissue biomarker for PTC malignancies and it may have potentials to become a noninvasive, blood-based biomarker for PTC diagnosis and evaluation of LN status. Show more

Keywords: microRNA-451, papillary thyroid carcinoma, diagnosis, lymph node metastasis

DOI: 10.3233/CBM-170059

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-9, 2017

Authors: Li, Jialin | Li, Ming | Gao, Feng | Ge, Xiaojun

Article Type: Research Article

Abstract: BACKGROUND: Clinical significance of microRNA (miR)-15a in human esophageal squamous cell carcinoma (ESCC) remains unclear. OBJECTIVE: To evaluate the expression level of miR-15a and to determine its potential for diagnosis and prognosis in ESCC. METHODS: Quantitative reverse transcription polymerase chain reaction was performed to examine the expression levels of miR-15a in ESCC tissues and patients' sera. The diagnostic and prognostic implications of serum miR-15a level in human ESCC were further evaluated. RESULTS: Expression levels of miR-15a in ESCC tissues and patients' sera were significantly decreased (both P< 0.001). Additionally, serum …miR-15a had an optimal diagnostic cut-off point (2.29) for ESCC with sensitivity of 86.36% and specificity of 100.00%. Moreover, low serum miR-15a level more frequently occurred in ESCC patients with advanced tumor-node-metastasis, T and N stages (all P= 0.01) and poor tumor differentiation (P= 0.03). The Kaplan-Meier curve showed that low miR-15a expression was significantly associated with shorter overall survival (OS) and disease-free survival (DFS) of ESCC patients (both P< 0.001). Further multivariate analysis identified miR-15a as an independent prognostic factor for both OS and DFS (both P= 0.01). CONCLUSION: Decreased expression of miR-15a may play a crucial role in ESCC development and progression. Serum miR-15a level could be used as a potential diagnostic and prognostic marker in clinics. Show more

Keywords: Esophageal squamous cell carcinoma, microRNA-15a, diagnosis, clinicopathological feature, prognosis

DOI: 10.3233/CBM-160667

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-7, 2016

Authors: Portich, Júlia Plentz | Gil, Mirela Severo | dos Santos, Rafael Pereira | Goulart, Bruno Kilpp | Ferreira, Maria Beatriz Cardoso | Loss, Jiseh Fagundes | Gregianin, Lauro José | Brunetto, Algemir Lunardi | Brunetto, André Tesainer | Roesler, Rafael | de Farias, Caroline Brunetto

Article Type: Research Article

Abstract: BACKGROUND: Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related receptor kinase B (TrkB) are involved in the maturation of B lymphocytes in the bone marrow (BM), promote cell differentiation in B-cell malignancies, and are associated with poor prognosis in adults with acute leukemia (AL). However, the role of BDNF in pediatric AL remains poorly understood. OBJECTIVE: We carried out a cohort observational study to evaluate BDNF levels in BM or peripheral blood (PB) samples from children with AL. METHODS: BM or PB samples were collected from 57 children and adolescents with acute lymphoid …leukemia (ALL), 14 children and adolescents with acute myeloid leukemia (AML), and 44 healthy individuals (HI) of the same age range. RESULTS: BDNF levels at diagnosis in AL patients were significantly lower when compared to HI. Samples from patients in complete remission from disease had higher levels of BDNF compared to those obtained from patients with malignant cells. Moreover, BDNF levels at diagnosis in patients who died were significantly lower compared to those found in survivors. CONCLUSIONS: These findings provide the first evidence for a possible role of BDNF as a marker of active disease and poor prognosis in pediatric AL. Show more

Keywords: Brain-derived neurotrophic factor, neurotrophin, acute lymphoid leukemia, acute myeloid leukemia

DOI: 10.3233/CBM-160646

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-6, 2016

Authors: Akyol, Murat | Alacacioglu, Ahmet | Demir, Leyla | Kucukzeybek, Yuksel | Yildiz, Yasar | Gumus, Zehra | Kara, Mete | Salman, Tarik | Varol, Umut | Taskaynatan, Halil | Oflazoglu, Utku | Bayoglu, Vedat | Tarhan, Mustafa Oktay

Article Type: Research Article

Abstract: BACKGROUND: In early breast cancer patients, the effects of hormonal therapy (tamoxifen and aromatase inhibitors) on plasma fibroblast growth factor 21 (FGF-21), lipid levels and body composition have not yet been investigated. Therefore, we aimed to analyze the relationship between FGF-21 and body composition as well as the effects of tamoxifen and aromatase inhibitors on plasma lipid levels, FGF-21, and body composition. METHODS: A total of 72 patients were treated with either tamoxifen or aromatase inhibitors due to their menopausal status after adjuvant radiotherapy. Each patient was followed-up over a period of 1 year. Changes in …body composition and serum lipid profile, glucose and FGF-21 levels were evaluated. We recorded the type of hormonal therapy, body mass index, waist-to-hip ratio, lipid profile, and FGF-21 levels both at the beginning and after 12 months. RESULTS: There was a statistically significant decrease in serum FGF-21 levels after 12 months of adjuvant endocrine therapy (46 ± 19.21 pg/ml vs. 30.99 ± 13.81 pg/ml, p< 0.001). Total body water (p< 0.001), serum glucose (p= 0.036) and triglyceride levels (p< 0.001) also exhibited a significant decrease. The decreases in total cholesterol and low-density lipoprotein were not statistically significant. Likewise, high-density lipoprotein increased after adjuvant endocrine therapy, although it did not reach statistical significance. The changes in body composition, glucose, lipid profile and FGF-21 were similar in tamoxifen and aromatase inhibitor groups. A positive correlation was found between basal weight, fat mass, fat-free mass and serum FGF-21 levels; however, the correlation was maintained only for the fat-free mass at the 12th month. CONCLUSION: As part of the present study, we suggest that both tamoxifen and aromatase inhibitors can reduce FGF-21 levels independently of body compositions, and these drugs can provide antihyperlipidemic, antidiabetic and cardio-protective effects. We also recommend that serum FGF-21 level can be utilized as a tumor biomarker in early-stage breast cancer and for monitoring purposes. FGF-21 levels may help physicians estimate prognosis, too. Further studies with larger populations may shed light on the role of FGF-21 in breast cancer. MINI ABSTRACT: In early breast cancer patients, we suggest that both TMX and AIs can reduce FGF-21 levels independently of body compositions, and these drugs can provide antihyperlipidemic, antidiabetic and cardio-protective effects.We also recommend that serum FGF-21 level can be utilized as a tumor biomarker in early-stage breast cancer and for monitoring purposes. FGF-21 levels may help physicians estimate prognosis, too. Further studies with larger populations may shed light on the role of FGF-21 in breast cancer. Show more

Keywords: Breast cancer, serum FGF 21, glucose metabolism, lipid metabolism, tamoxifen, aromatase inhibitors

DOI: 10.3233/CBM-161507

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-9, 2017

Authors: Pietrusiński, Michaƚ | Képczyński, Ƚukasz | Jédrzejczyk, Adam | Borkowska, Edyta | Traczyk-Borszyńska, Magdalena | Constantinou, Maria | Kaƚużewski, Bogdan | Borowiec, Maciej

Article Type: Research Article

Abstract: BACKGROUND: Promoter hypermethylation can be a useful biomarker for early detection and prognosis of bladder cancer, monitoring response to treatment and complement classical diagnostic procedures. OBJECTIVE: The molecular test was performed on DNA from bladder cancer cells in voided urine samples, tumor tissue DNA and normal control DNAs. We aimed to assess the diagnostic potential of epigenetic changes in urine DNA from bladder cancer cases at various clinico-pathological stages of the disease. METHODS: The methylation status of 5 genes (p14ARF, p16INK4A, RASSF1A, DAPK, APC ) in 113 tumor samples paired with voided …urine specimens was analyzed by MSP. We compared the results of methylation analysis with UroVysion test. RESULTS: The methylation profile in tumor/urine DNA was significantly correlated (p ≤ 0,05) with tumor grade in p14ARF , RASSF1a , APC /p14ARF , APC genes, respectively and with stage in p14ARF , RASSF1a /p14ARF genes, respectively. The results of UroVysion test were in correlation with hypermethylation both in tumor and urine DNA in p14ARF , RASSF1a and APC genes (p = 0,008; 0,02 and 0,04, respectively). CONCLUSIONS: Promoter hypermethylation of tumor suppressor genes is a frequent mechanism in bladder cancer. We found promoter hypermethylation in all grades and stages of all cases examined. Methylation profile of selected suppressor genes may be a potential useful biomarker and enhance early detection of bladder cancer using a noninvasive urine test. Show more

Keywords: Bladder cancer, DNA methylation, cancer epigenetics

DOI: 10.3233/CBM-160673

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-13, 2016

Authors: Formica, Vincenzo | Morelli, Cristina | Ferroni, Patrizia | Nardecchia, Antonella | Tesauro, Manfredi | Pellicori, Stefania | Cereda, Vittore | Russo, Antonio | Riondino, Silvia | Guadagni, Fiorella | Roselli, Mario

Article Type: Research Article

Abstract: BACKGROUND: High Neutrophil/Lymphocyte ratio (NLR), as a measure of enhanced inflammatory response, has been negatively associated with prognosis in patients with localized pancreatic ductal adenocarcinoma (PDA). OBJECTIVE: In the present study, we aimed at investigating the prognostic value of NLR in two homogeneous groups of chemotherapy-naïve metastatic PDA patients. Patients were treated with either gemcitabine (GEM) or gemcitabine/oxaliplatin (GEMOXA). We also assessed whether NLR could identify patients benefiting from the use of oxaliplatin. METHODS: Consecutive PDA patients treated at the Medical Oncology Unit of Tor Vergata University Hospital of Rome with either GEM …or GEMOXA were included (n= 103). NLR was assessed before and during chemotherapy and correlated with outcome together with common clinical and biochemical variables. RESULTS: Among 17 analyzed variables NLR, Karhofsky Perfomance Status (KPS), d-dimer and erythrocyte sedimentation rate were found to be significantly associated with median Overall Survival (mOS) at the univariate analysis. Only NLR and KPS were independent prognosticator at multivariate analysis, with NLR displaying the highest statistical significance. NLR was also predictive of oxaliplatin activity, as only patients with NLR > 2.5 (cutoff determined upon ROC analysis) derived benefit from GEMOXA over GEM. CONCLUSIONS: NLR is both an independent prognostic and predictive factor in metastatic PDA, since only patients with high NLR seem to benefit from the addition of oxaliplatin. NLR may help select patients for whom a particularly poor prognosis might justify more intensive, yet less tolerable, combination regimens. Show more

Keywords: Neutrophil/lymphocyte ratio, pancreatic ductal adenocarcinoma, gemcitabine, oxaliplatin

DOI: 10.3233/CBM-160645

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-11, 2016

Authors: Hu, Jianxia | Li, Chengqian | Liu, Chongkai | Zhao, Shihua | Wang, Yangang | Fu, Zhengju

Article Type: Research Article

Abstract: BACKGROUND: The sensitivity and specificity of biomarkers which have been used in clinical practice for diagnosis of papillary thyroid carcinoma (PTC) are low, it is essential to develop novel diagnostic and prognostic biomarkers for PTC. OBJECTIVE: To explore the expressions of miR-940, miR-15a, miR-16 and IL-23 in PTC tissues and plasma and their associations with the clinical characteristics of PTC. METHODS: We investigated the expressions of miR-940, miR-15a, miR-16 and IL-23 in plasma and thyroid tissues of PTC, nodular goiter and healthy people with qRT-PCR, and further analyzed the associations between their levels …and the clinical characteristics of PTC. RESULTS: Level of IL-23 expression was higher while levels of miR-940, miR-15a and miR-16 expression in the PTC tissues were lower compared with the nodular goiter tissues and perineoplastic thyroid tissues. And the levels of miR-940, miR-15a, miR-16 and IL-23 expression in the PTC tissues were associated with some clinical characteristics of PTC, including bilateral tumor, multicentricity, extrallyroidal invasion, cervical lymph node metastasis, distant metastasis and clinical advanced stages (III/IV). CONCLUSIONS: Expressions of miR-940, miR-15a, miR-16 and IL-23 in PTC tissues might be useful biomarkers and promising targets in the diagnosis of papillary thyroid carcinoma. Show more

Keywords: Papillary thyroid carcinoma, miR-940, miR-15a, miR-16, IL-23

DOI: 10.3233/CBM-161723

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-8, 2016

Authors: Guo, Yunsheng | Pang, Yan | Gao, Xia | Zhao, Min | Zhang, Xin | Zhang, Hao | Xuan, Bing | Wang, Yimin

Article Type: Research Article

Abstract: The mechanisms underlying oxaliplatin (OXA) resistance in colon cancer cells are not fully understood. MicroRNAs (miRNAs) play important roles in tumorigenesis and drug resistance. However, the relationship between miRNA and OXA resistance in colon cancer cells has not been previously explored. In this study, we utilized microRNA microarray analysis and real-time PCR to verify that miR-93, miR-191, miR-137, miR-181 and miR-491-3p were significantly down-regulated and that miR-96, miR-21, miR-22, miR-15b and miR-92 were up-regulated in both HCT-15/OXA and SW480/OXA cell lines. Blocking miR-137 caused a significant inhibition of OXA-induced cytotoxicity, therefore, miR-137 was chosen for further research. An in vitro …cell viability assay showed that knockdown of miR-137 in HCT-15 and SW480 cells caused a marked inhibition of OXA-induced cytotoxicity. Moreover, we found that miR-137 was involved in repression of YBX1 expression through targeting its 3'-untranslated region. Furthermore, down-regulation of miR-137 conferred OXA resistance in parental cells, while over-expression of miR-137 sensitized resistant cells to OXA, which was partly rescued by YBX1 siRNA. The results of this study may aid the development of therapeutic strategies to overcome colon cancer cell resistance to OXA. Show more

Keywords: Colon cancer, miR-137, YBX1, drug resistance

DOI: 10.3233/CBM-160650

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-9, 2016

Authors: Kurtul, Neslihan | Taşdemir, Erdem Arzu | Ünal, Dilek | İzmirli, Mustafa | Eroglu, Celalettin

Article Type: Research Article

Abstract: BACKGROUND: The aim of this study is to search the prognostic value of SPARC expression in rectum cancer cases receiving postoperative radiotherapy. METHODS: Forty three rectal cancer patients are recruited to this retrospective study. All patients received postoperative radiotherapy which the median dose was 5040 cGy and concomitant chemotherapy. Samples taken from their paraffin blocks were examined with immunohistochemical procedures. RESULTS: When the association between SPARC expression and the clinicopathological feature was examined, there was a significant association between age and expression levels. Overall survival of patients with low expression was found to …be 67 months whereas the overall survival of the patients with high expression was 32 months and the difference was statistically significant. Time to local recurrence of patients with low expression was found to be 74 months whereas time to local recurrence of the patients with high expression was 31 months. Progression free survival of the patients with low expression and high expression were 67 months and 32 months, respectively. In multivariate Cox regression analyses, high expression of SPARC was found to be associated with a statistically significant shorter overall survival and progression free survival. CONCLUSIONS: High expression of SPARC is related to worse prognosis in rectal cancer patients. Show more

Keywords: Prognosis, rectal cancer, SPARC

DOI: 10.3233/CBM-161733

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-9, 2016

Authors: Yang, Zhao-Yang | Yang, Fang | Zhang, Ying-Li | Liu, Bao | Wang, Meng | Hong, Xuan | Yu, Yan | Zhou, Yao-Hui | Zeng, Hai

Article Type: Research Article

Abstract: Our study aimed to explore the effects of long noncoding RNA (lncRNA)-ANCR on the invasion and migration of colorectal cancer (CRC) cells by regulating enhancer of zeste homolog 2 (EZH2) expression. CRC tissues and adjacent normal tissues were collected and CRC SW620 cells line and normal human intestinal epithelial cells (HIECs) were incubated. CRC SW620 cells line was transfected with ANCR-siRNA. The expressions of ANCR and EZH2 mRNA were measured by real-time quantitative polymerase chain reaction (RT-qPCR). EZH2 and trimethylation of H3K27 (H3K27me3) protein expressions were detected using Western blotting. The relationship between ANCR and EZH2 was determined through RNA …pull-down and co-immunoprecipitation (co-IP) assays. Cell invasion and migration were determined by Trans-well and cell scratch assays. ANCR, EZH2 and H3K27me3 expressions were up-regulated in CRC tissues and SW620 cells (all P < 0.05). After transfected with ANCR-siRNA, SW620 cells showed decreased ANCR expression and EZH2 mRNA and protein expressions (all P < 0.05). According to the results of RNA pull-down and co-IP assays, ANCR could specifically bind to EZH2. The results of Trans-well and cell scratch tests showed that when ANCR expression was decreased, the invasion and migration abilities of SW620 cells significantly declined (both P < 0.05). In conclusion, these results suggest that lncRNA-ANCR could influence the invasion and migration of CRC cells by specifically binding to EZH2. Show more

Keywords: LncRNA, ANCR, EZH2, invasion, migration, colorectal cancer

DOI: 10.3233/CBM-161715

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-10, 2016

Authors: Chen, Xiaoxi | Lai, Xiangwen | Wu, Caixia | Tian, Qingxin | Lei, Tingting | Pan, Jingye | Huang, Guoyu

Article Type: Research Article

Abstract: BACKGROUND: Members of the SIRT family are a highly conserved family of NAD + -dependent enzymes, many of which (SIRT1-7) play an important role in tumor formation. Recently, several studies have suggested that SIRT4 not only regulates glutamine metabolism, but also serves as a tumor suppressor. There are no studies have assessed its clinical significance in endometrioid adenocarcinoma. METHODS: We investigated SIRT4 protein levels in endometrioid adenocarcinoma and its possible association with selected clinico-pathological parameters by immunohistochemical staining of a tissue microarray that included 65 endometrioid adenocarcinoma patients. RESULTS: SIRT4 …protein levels in endometrioid adenocarcinoma were markedly lower than its non-neoplastic tissue counterpart (P < 0.001). Moreover, lower SIRT4 expression levels were observed in advanced AJCC stages of development (P = 0.002). CONCLUSIONS: Our results indicated that SIRT4 may be involved in the development of endometrioid adenocarcinoma and is a promising target for both the diagnosis and potential therapy of endometrioid adenocarcinoma. Show more

Keywords: Endometrioid adenocarcinoma, endometrium, sirtuin, SIRT4

DOI: 10.3233/CBM-160419

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-6, 2017

Authors: Dou, Chunqing | Jin, Xin | Sun, Liyuan | Zhang, Bao | Han, Mingming | Li, Tao

Article Type: Research Article

Abstract: OBJECTIVE: The transcription factor FOXF2 is reported to be down-regulated in HCC. Its deficiency is correlated with shorter disease-free survival and overall survival of HCC patients; however, the mechanism remains to be elucidated. MATERIALS AND METHODS: In this study, we performed qRT-PCR and western blotting to confirm the down-regulated FOXF2 in HCC tissue and cell lines. Then the HCC cell line Huh7 transduced with FOXF2 shRNA was adopted in a series of in vitro and in vivo assays to evaluate the cell phenotype change, migration, invasion, proliferation, colonization of circulating cell and the formation of …metastatic nodules. RESULTS: We found that FOXF2 was down-regulated in HCC tissues and cell lines. FOXF2 deficiency in Huh7 cells increased E-cadherin and decreased Vimentin. The down-regulation of FOXF2 impeded HCC cell migration and invasion capacity, but promoted the proliferation of HCC cells and the growth of subcutaneous tumors in nude mice, which indicated a mesenchymal-to-epithelial phenotypic change in Huh7 cells. FOXF2 deficiency enhanced the colonization of circulating HCC cell, thus promoted the formation of metastatic nodules. CONCLUSIONS: FOXF2 deficiency induced mesenchymal-epithelial transition (MET) in Huh7 cell which might facilitate the colonization of circulating tumor cells and the formation of metastasis. Show more

Keywords: Hepatocellular carcinoma (HCC), metastasis, forkhead box F2 (FOXF2), mesenchymal-epithelial transition (MET)

DOI: 10.3233/CBM-170139

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-8, 2017

Authors: Soheili, Saamaaneh | Asadi, Malek Hossien | Farsinejad, Alireza

Article Type: Research Article

Abstract: BACKGROUND: OCT4 is a key regulator of self-renewal and pluripotency in embryonic stem cells which can potentially encode three spliced variants designated OCT4A, OCT4B and OCT4B1. Based on cancer stem cell concept, it is suggested that the stemness factors misexpressed in cancer cells and potentially is involved in tumorigenesis. OBJECTIVE: Accordingly, in this study, we investigated the potential expression of OCT4 variants in breast cancer tissues. METHODS: A total of 94 tumoral and peritumoral breast specimens were evaluated with respect to the expression of OCT4 variants using quantitative RT-PCR and immunohistochemical (IHC) analysis. …RESULTS: We detected the expression of OCT4 variants in tumor tissues with no or very low levels of expression in peritumoral samples of the same patients. While OCT4B was highly expressed in lobular type of breast cancer, OCT4A and OCTB1 variants are highly expressed in low grade (I and II) ductal tumors. Furthermore, the results of this study revealed a considerable association between the expression level of OCT4 variants and the expression of ER, PR, Her2 and P53 factors. CONCLUSIONS: All data demonstrated a distinctive expression pattern of OCT4 spliced variants in different types of breast cancer and provide further evidence for the involvement of embryonic genes in carcinogenesis. Show more

Keywords: OCT4 spliced variants, cancer stem cells, breast cancer

DOI: 10.3233/CBM-160675

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-8, 2016

Authors: Maimaiti, Yusufu | Dong, Lingling | Aili, Aikebaier | Maimaitiaili, | Huang, Tao | Abudureyimu, Kelimu

Article Type: Research Article

Abstract: BACKGROUND: Bcl-2 interacting mediator of cell death (Bim) appears to have contradictory roles in cancer. It is uncertain whether Bim show prognostic significance in patients with breast cancer. OBJECTIVE: To investigate the correlation between Bim expression and clinicopathological characteristics of breast cancer and to evaluate Bim’s effect on overall survival (OS). METHODS: We used immunohistochemistry (IHC) technique to detect the expression of Bim via tissue microarray in 275 breast cancer samples, Kaplan-Meier analysis to perform survival analysis, and Cox proportional hazards regression model to explore the risk factors of breast cancer. …RESULTS: The results revealed that Bim expression was significantly correlated with age, estrogen receptor (ER) and/or progesterone receptor (PR), human epidermal growth factor receptor (HER2) and Ki67 expression (P < 0.05). Bim expression was significantly different in the four molecular subtypes (P = 0.000). Survival analysis showed that Bim positive expression contributed to a shorter OS (P = 0.034), especially in patients with luminal A tumors (P = 0.039). Univariate and multivariate regression analysis showed that Bim was an independent prognostic factor for breast cancer (P < 0.05). CONCLUSION: Bim may serve as an effective predictive factor for lower OS in breast cancer patients, especially in those with luminal A tumors. Show more

Keywords: Bim, breast cancer, biomarker, prognosis, luminal A

DOI: 10.3233/CBM-160377

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-8, 2017

Authors: Shi, Shengjun | Tian, Binqun

Article Type: Research Article

Abstract: BACKGROUND: Bladder cancer is one of the most common genitourinary malignancies, with a high rate of recurrence and progression. The prognosis for patients with bladder cancer, especially muscle-invasive bladder cancer, remains poor despite systemic therapy. OBJECTIVE: To explore the underlying disease mechanisms and identify more effective biomarkers for bladder cancer. METHODS: Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis were applied to identify hub genes correlated with the bladder cancer progression. Survival analyses were then conducted to identify potential biomarkers correlated with the prognosis of bladder cancer. Finally, validation …and analysis of these potential biomarkers were conducted by a series of bioinformatics analyses. RESULTS: Based on the results of weighted gene co-expression network analysis and protein-protein interaction network analysis, ten hub genes closely correlated with bladder cancer progression were identified in the relevant module. Survival analyses of these genes indicated that elevated expressions of six potential biomarkers (COL3A1, FN1, COL5A1, FBN1, COL6A1 and THBS2 ) were significantly associated with a worse overall survival. Furthermore, these 6 potential biomarkers were validated in association with the progression of bladder cancer. Bladder cancer samples with higher expression of these genes were most significantly enriched in gene set associated with ECM-receptor interaction. CONCLUSIONS: This study identified several biomarkers associated with bladder cancer progression and prognosis. As novel findings, these may have important clinical implications for diagnosis, treatment and prognosis prediction. Show more

Keywords: Bladder cancer, weighted gene co-expression network analysis (WGCNA), biomarkers, progression, prognosis

DOI: 10.3233/CBM-181940

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Yan, Lin | Yu, Hai-Hua | Liu, Yuan-Shui | Wang, Yan-Sen | Zhao, Wen-Hua

Article Type: Research Article

Abstract: BACKGROUND: Colorectal cancer (CRC) is the most common malignant disease worldwide and thus new therapeutic approaches are needed. 5-Fluorouracil (5-FU) remains the most widely used agent to treat colorectal cancer (CRC). However, its clinical efficacy is currently limited by the development of drug resistance. Esculetin (EST), a coumarin, was found to have anti-proliferative and anti-migration activity in cancer. OBJECTIVE: This research aims to evaluated the influence and possible mechanism of EST on the proliferation, migration and epithelial-mesenchymal transition of CRC cell lines. MATERIALS AND METHODS: Human CRC cell lines HT-29, SW480, HCT-116, and …Caco-2 were treated with various concentrations of EST (0.2, 2, 20, 200, 2000 μ g/ml) or 5-FU (0.1, 1, 10, 100, 1000 μ g/ml) for 48 h, and cell viability was determined by the MTT and CCK-8 assay. The motility of HCT-116 cells was detected by scratch assay. Western blot was applied to detect the protein expression. Besides, levels of Wnt3a and VEGF in HCT-116 cell culture medium supernatant were analyzed by ELISA. The anti-tumor effect was detected with HCT-116 subcutaneous tumor bearing tumor model by monitoring the tumor vomume in vivo . Finally, the tumoral expression of VEGF was measured by immunohistochemistry, and the expression of Ki67, PCNA, β -catenin, c-Myc, Cyclin D1, MMP2 and MMP7 was measured by Western blot analysis. RESULTS: EST inhibited HCT-116 cell proliferation in a dose-dependent manner. Western blot analysis revealed that EST decreased the expression of Ki67, PCNA, N-cadherin, E-cadherin, vimentin, fibronectin, β -catenin, c-Myc, Cyclin D1, MMP2 and MMP7. Furthermore, EST reduced the release of Wnt3a and VEGF into HCT-116 cells culture medium. After EST treatment, the tumor volume was significant smaller than that of the control group, and the tumoral levels of VEGF were decreased. Moreover, western blot analysis indicated that the expression of Ki67, PCNA, β -catenin, c-Myc, Cyclin D1, MMP2 and MMP7 were also significantly decreased after treated with EST. In addition, in vitro and in vivo anti-tumor results demonstrated that EST combined with 5-FU could increase the inhibitory effect of 5-FU on HCT-116 cells proliferation, migration and epithelial-mesenchymal transition. CONCLUSIONS: EST enhances the inhibitory effect of 5-FU on the proliferation, migration and epithelial-mesenchymal transition of CRC. Show more

Keywords: EST, CRC, proliferation, migration, epithelial-mesenchymal transition

DOI: 10.3233/CBM-181764

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-10, 2019

Authors: Li, Hang | Pan, Xiang | Quan, Jing | Li, Zuwei | Zhao, Liwen | Guan, Xin | Xu, Jinling | Xu, Weijie | Gui, Yaoting | Lai, Yongqing

Article Type: Research Article

Abstract: OBJECTIVE: Renal cell carcinoma (RCC) is one of the most common genitourinary cancers, and advanced RCC usually leads to poor prognosis. Therefore, identifying novel biomarkers for predicting the progression and prognosis of RCC is essential. The present study aims to evaluate the clinical value of miR-183-5p in RCC development and prognosis after surgery. MATERIALS AND METHODS: We enrolled a total of 284 patients who received partial or radical nephrectomy from April 2003 to May 2013 at a single institution. The clinical and pathological characteristics of the patients were collected, including age, gender, tumor size, tumor stage, …as well as follow-up information. The expression levels of miR-183-5p of all the patients were calculated from FFPE specimens. Cox regression analyses were performed to approve the effect of miR-183-5p expression on patient survival. Kaplan-Meier method was used to analyze the patient survival curves. RESULTS: After controlling for gender, age, tumor size and tumor stage in the multivariate analysis, we found that high expression of miR-183-5p was independently associated lower overall survival (HR = 0.550, 95% CI = 0.364–0.832, p = 0.005). The Kaplan-Meier analysis also showed that patients with high expression of miR-183-5p had a significantly poor prognosis (p = 0.006). These results was verified by analyzing the data of 506 cases from The Cancer Genome Atlas database (TCGA). CONCLUSION: Our results indicated that the high miR-183-5p expression is an independent factor for predicting RCC’s worse prognosis. Show more

Keywords: MicroRNAs, miR-183-5p, renal cell cancer, oncogene, prognosis biomarkers

DOI: 10.3233/CBM-182047

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-6, 2019

Authors: Wei, Juan | Wei, Wei | Xu, Hanfeng | Wang, Zhaojing | Gao, Wen | Wang, Tianjun | Zheng, Qin | Shu, Yongqian | De, Wei

Article Type: Research Article

Abstract: BACKGROUND: Circular RNAs (circRNA) play key regulatory roles in cancer progression. Human circRNA microarray was performed to screen for abnormally expressed circRNA in gastric cancer tissues. In this study, we found circRNA102958 was up-regulated in gastric cancer tissues and cell lines. METHODS: The hsa_circRNA_102958 levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in gastric tissue and cell. Then, the association between the expression level of hsa_circRNA_102958 and the clinicopathological features of patients with gastric cancer was further analyzed. Finally, a network of hsa_circRNA_102958-miRNA-mRNA interactions was predicated. RESULTS: In this study, we …analyzed 30 patients and found that hsa_circRNA_102958 was significantly overexpressed in gastric cancer tissues compared with paired adjacent normal tissues. Clinicopathological features showed that hsa_circRNA_102958 level in GC tissues was positively associated with TNM stage (p = 0.032). The area under the ROC curve was 0.74. Finally, a total of 5 miRNAs were predicted to have an interaction with hsa_circRNA_102958. CONCLUSIONS: hsa_circRNA_102958 may be a potential novel and stable biomarker for the diagnosis of gastric carcinoma. Show more

Keywords: Gastric cancer, hsa_circRNA_102958, diagnosis, miRNA, mRNA

DOI: 10.3233/CBM-182029

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-7, 2019

Authors: Ji, Bing | Huang, Youmin | Gu, Ting | Zhang, Li’e | Li, Guohong | Zhang, Changgeng

Article Type: Research Article

Abstract: BACKGROUND: Plasma carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 72-4 (CA72-4) are common markers which are useful in the diagnosis and prognosis of GC. However, their sensitivity and specificity in GC remain unsatisfactory. Identification of cancer diagnosed-biomarkers would be of great value. OBJECTIVE: Evaluate the diagnostic and prognostic value of LINC00086 and miR-214 in GC. METHODS: In this study, we determined the expression of LINC00086 and miR-214 in GC by qRT-PCR. Additionally, we investigated the relationship between various clinicopathological features of GC patients and LINC00086 or miR-214 expression, and evaluated the diagnostic …and prognostic value of LINC00086 and miR-214 in GC. RESULTS: In this study, we found that plasma LINC00086 expression was significantly lower, whereas plasma miR-214 expression was significantly higher in GC patients than in normal individuals. LINC00086 and miR-214 exhibited high sensitivity and specificity in diagnosing GC. Additionally, GC patients with low LINC00086 or high miR-214 expression were likely to have larger tumors, lymphatic metastasis, larger TNM stage, and higher CEA and CA19-9 levels. Moreover, GC patients with low LINC00086 or high miR-214 expression showed lower survival rates. Lymphatic metastasis, LINC00086, and miR-214 are independent factors affecting patient diagnosis. CONCLUSIONS: LINC00086 and miR-214 are potentially diagnostic and prognostic markers for GC. Show more

Keywords: Gastric cancer, LINC00086, miR-214, diagnosis, prognosis

DOI: 10.3233/CBM-181486

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-7, 2019

Authors: Pasha, Heba F. | Mohamed, Randa H. | Radwan, Mohamed I.

Article Type: Research Article

Abstract: BACKGROUND: DNA methylation status is one of the most prevalent molecular alterations in human cancers. Identification of powerful diagnostic and prognostic biomarkers for hepatocellular carcinoma (HCC) without a biopsy is urgently required. OBJECTIVE: The purpose of this study was to determine the methylation status of RASSIF1A and SOCS-1genes as a non-invasive biomarker for HCC identification and prognosis. METHODS: Methylation specific-PCR technique was performed to recognize the methylation status of RASSIF1A and SOCS-1 genes in 100 patients with HCC, 100 patients with liver cirrhosis (LC) but without HCC were considered as cirrhotic liver control …group and 100 healthy control. RESULTS: Methylation of RASSF1A and SOCS-1 genes were detected in 40% and 38% of HCC patients respectively, 14% and 20% of LC patients respectively. Methylation of SOCS-1 gene in peripheral blood of healthy control was 23%. Methylation of RASSF1A gene was associated with age, tumor size, vascular invasion and α fetoprotein (AFP), while SOCS-1 gene methylation was significantly associated with tumor size and AFP. Furthermore, using RASSF1A/ SOCS-1/ AFP panel improve diagnostic sensitivity for HCC 86% and specificity of 75%. CONCLUSION: RASSF1A and SOCS1genes methylation status may play an important role in the process of hepatocarcinogenesis and may be used as diagnostic and prognostic noninvasive biomarkers for HCC when combined with serum AFP. Show more

Keywords: Hepatocellular carcinoma, methylation, SOCS-1, RASSIF1A

DOI: 10.3233/CBM-181638

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-7, 2019

Authors: Ziai, Hedyeh | Alenazi, Abdulrahman | Hearn, Matthew | O’Connell, Daniel A. | Puttagunta, Lakshmi | Barber, Brittany | Harris, Jeffrey R. | Seikaly, Hadi | Biron, Vincent L.

Article Type: Research Article

Abstract: BACKGROUND: The role of molecular biomarkers in oropharyngeal squamous cell carcinoma (OPSCC) has recently been increasingly recognized. There is conflicting evidence in the literature with regards to the prognostic value of p53 and Bcl-xL. OBJECTIVE: The purpose of this study was to investigate the association between p53 and Bcl-xL expression profiles and survival outcomes in OPSCC. METHODS: Patients diagnosed with OPSCC and treated with curative intent between 1998 and 2009 were included in the study. Patient demographics, disease, treatment, and oncologic outcomes were collected prospectively. A tissue microarray (TMA) from patients’ biopsies or …surgical specimens was retrospectively constructed. The expression levels of p53, Bcl-xL, and p16 were digitally quantified and correlated to patient survival outcomes. RESULTS: One hundred and sixty-six patients were included (mean age 56.7 years; standard deviation (SD) ± 10.0; 78% male). High expression of Bcl-xL (p = 0.04) was significantly associated with nodal disease at presentation, and decreased overall survival (OS) (p = 0.04). Combined expression of low Bcl-xL and low p53 conferred a survival advantage in non-smokers (p = 0.04). Multivariate analysis supported smoking and p16 status as independent prognosticators for OS. CONCLUSIONS: This study suggests that biomarker profiling using Bcl-xL and p53 levels may be of prognostic value in select patients with OPSCC. Show more

Keywords: Oropharyngeal cancer, squamous cell carcinoma, p53, Bcl-XL, biomarkers, survival, recurrence

DOI: 10.3233/CBM-182106

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-11, 2018

Authors: Wang, Jin-Rong | Liu, Bin | Zhou, Lei | Huang, Yue-Xin

Article Type: Research Article

Abstract: BACKGROUND: A growing body of studies has demonstrated the aberrant expression of microRNAs (miRNAs) contributes to human tumor metastasis. MicroRNA-124-3p (miR-124-3p), which is down-regulated in various cancers, has been found to be involved in several signaling pathways relevant to tumor cell migration and invasion. However, the roles of miR-124-3p in human bladder cancer remain unclear. This study aims to investigate the functional significance of miR-124-3p and to understand how it targets the integrin receptor, and thus affects the progression of human bladder cancer. METHODS: Clinical specimens from 36 patients and three human bladder cancer cell lines …were analyzed for miR-124-3p and integrin α 3 (ITGA3) . To investigate the effects of miR-124-3p and ITGA3 on proliferation of bladder cancer cells, the MTT assay, colon-formation assay and flow cytometry were performed. In addition, wound healing assay and transwell assay were carried out to examine the migration and invasion of the bladder cancer cells transfected with miR-124-3p mimics or si-ITGA3. The luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were applied to validate the miR-124-3p directly binding with ITGA3. Finally, western blot was used to examine the expression level of the proteins involved in FAK/PI3K/AKT and FAK/Src signal pathway as well as epithelial-mesenchymal transition (EMT) process. RESULTS: The down-regulation of miR-124-3p and up-regulation of ITGA3 were observed in clinical specimens and bladder cancer cell lines. Overexpression of miR-124-3p or silencing ITGA3 inhibited tumor cell migration and invasion. Luciferase assay confirmed miR-124-3p directly targets ITGA3, and western blot suggested that miR-124-3p plays a crucial role in the EMT and metastasis of human bladder cancer through FAK/PI3K/AKT and FAK/Src signaling mechanism. Also, by targeting ITGA3, miR-124-3p can modulate the expression of N- and E-cadherin, and thus inhibit the EMT. CONCLUSIONS: By targeting ITGA3 and downstream FAK/PI3K/AKT and FAK/Src signaling pathways, miR-124-3p suppresses cell migration and invasion in bladder cancer. Our study reasonably speculates that miR-124-3p can be potentially developed as a therapeutic target and prognostic biomarker for bladder cancer. Show more

Keywords: Bladder cancer, miR-124-3p, ITGA3, FAK/PI3K/AKT, EMT

DOI: 10.3233/CBM-182000

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-13, 2018

Authors: Shen, Mingjing | Cai, Lichun | Jiang, Kanqiu | Xu, Weihua | Chen, Yongbin | Xu, Zhongheng

Article Type: Research Article

Abstract: Lung cancer represents a major healthy concern due to high incidence and morality. Increasing evidences showed critical regulatory role of microRNA (miR) in cell growth, differentiation and apoptosis. It has been indicated that the level of miR-328 is abnormally up regulated in lung cancer cell line, which is correlated with cell apoptosis. An in vitro lung cancer model was established through induction of chlamydia pneumonia. Western blot and real-time quantitative PCR were used to measure miR-328 level and its effects on histone H2AX expression. Bioinformatics analysis and luciferase reporter gene assay were to determine if H2AX was the direct …target of miR-328. TUNEL assay, AV-PI staining and Caspase-3 activity assay measured the effect of the decrease of miR-328 on lung cancer cell apoptosis at both in vivo and in vitro level. Bioinformatics analysis predicted histone H2AX as the target of miR-328 during the regulation of lung cancer. Both in vivo and in vitro knockdown of miR-328 up-regulated H2AX expression and elevated TUNEL-positive cell number. In vivo down-regulation of miR-328 decreased incidence of lung cancer induced by chlamydia pneumoniae, suppressed tumor volume, increased caspase 3 activity, and facilitated tumor cell apoptosis. Histone protein H2AX serves as the target of miR-328 and participates in lung cancer regulation. Suppression of miR-328 level promotes lung cancer tissue apoptosis, which provides novel target for lung cancer therapy. Show more

Keywords: Lung cancer, miR-328, histone protein H2AX

DOI: 10.3233/CBM-181999

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-8, 2018

Authors: Feng, Youfan | Zhang, Yuxia | Wei, Xiaofang | Zhang, Qike

Article Type: Research Article

Abstract: OBJECTIVE: Human multiple myeloma (MM) is a kind of common tumor in middle-aged and elderly people, in which the osteolytic lesion is formed mainly through inhibiting osteoblast (OB) differentiation and promoting osteoclast (OC) differentiation. Dickkopf-1 (DKK1) is a soluble Wnt inhibitor, which has an important correlation with the pathogenesis of human MM. Therefore, the correlations of DKK1 with pathogenesis and prognosis of human MM were investigated in this study. METHODS: The DKK1 expression in tissues and serum of myeloma patients was detected via immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Correlation between DKK1 expression and survival time …of patients was analyzed via Kaplan-Meier analysis. To further study the mechanism of DKK1 expression in pathogenesis and prognosis of human MM, MM cells were treated with DKK1 neutralizing antibody (BHQ880) or transfected with DKK1-small-interfering ribonucleic acid (siRNA) to study its effects on OB differentiation, osteocalcin level, β -catenin and interleukin-6 (IL-6) secretion. Moreover, the effect of DKK1-siRNA transfection on the activity of U266 cells was detected via methyl thiazolyl tetrazolium (MTT) assay. RESULTS: The DKK1 expression in tissues and serum of myeloma patients was significantly higher than that in control group (p < 0.01). In terms of survival time, the median survival time (45 months) in patients with low DKK1 expression was significantly longer than that in patients with high DKK1 expression (only 22 months). The DKK1 neutralizing antibody (BHQ880) and DKK1-siRNA significantly reduced the DKK1 level in MM cells, promoted the OB differentiation, increased the osteocalcin deposition, promoted the β -catenin expression and decreased the IL-6 expression and β -catenin phosphorylation. DKK1-siRNA could also reduce the proliferative activity of MM cells. CONCLUSION: DKK1 is closely related to the pathogenesis and prognosis of human MM, which might be a potential biomarker for the diagnosis of MM. Show more

Keywords: DKK1, human multiple myeloma, pathogenesis, prognosis

DOI: 10.3233/CBM-181909

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-7, 2018

Authors: Wang, Zhibin | Zhao, Xuan | Ma, Zhiming | Liu, Li | Wang, Bin | Li, Yuan

Article Type: Research Article

Abstract: Gallbladder carcinoma (GC) occupies more than 90% of all cancers in biliary tract with an increasing incidence. Most patients with GC are already at terminal stage at the time of primary diagnosis, causing unfavorable prognosis and high mortality. Transformation growth factor-beta (TGF-β ) is up-regulated in GC. However, the mechanism by how TGF-β is involved in GC remains unclear. The aim of this study was to investigate the effect and mechanism of TGF-β in GC using GC cell line NOZ cells. In vitro cultured NOZ cell was randomly assigned into …control, si-NC and TGF-β 1 siRNA groups and were transfected with siRNA negative control (NC) or TGF-β 1 siRNA followed by analysis of TGF-β 1 expression by Real-time PCR, cell proliferation by MTT assay, cell apoptosis and cell invasion, as well as expression of proteins in epithelial-mesenchymal transition (EMT), p38, Smad2/3 and Smad4 phosphorylation by Western blot, Insulin-like growth factor-binding protein-2 (IGFBP-2) level by ELISA. After transfecting TGF-β 1 siRNA into NOZ cells, TGF-β 1 expression was suppressed and cell proliferation and invasion were inhibited, together with enhanced Caspase-3 activity. Meanwhile, E-cadherin expression was increased, with decreased Vimentin, IGFBP-2, p38, Smad2/3 and Smad4 phosphorylation (P < 0.05 comparing to control group). In conclusion, inhibition of TGF-β 1 expression facilitates GC cell apoptosis, inhibits GC cell proliferation, invasion and EMT occurrence. Show more

Keywords: TGF-β1, gallbladder carcinoma, IGFBP-2/p38 pathway, EMT, proliferation

DOI: 10.3233/CBM-181895

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-7, 2018

Authors: Hou, Dongliang | Fang, Tong | Song, Linan | Sun, Baojin | Liu, Bo | Chen, Li

Article Type: Research Article

Abstract: Oral squamous cell carcinoma (OSCC) is a complex disease with extensive genetic and epigenetic defects, including microRNA deregulation. The aims of the present study were to explore the regulatory mechanism of microRNA-18a in OSCC cells proliferation and metastasis. Quantitative real-time PCR (qRT-PCR) was used to detect the expression level of miR-18a and KLF4 mRNA in OSCC tissues and cell lines (SCC-25, CAL-27, Tca-8113). Western-blot analysis was used to validate expression of KLF4 protein. CCK-8 assay was performed to e validate the proliferous ability of human OSCC cells. Transwell assays were performed to determine the migratory and invasive abilities of OSCC …in vitro . Dual-luciferase reporter assay, qRT-PCR and Western-blot were used to confirm that miR-18a regulates KLF4 expression in OSCC. miR-18a was significantly up-regulated in human OSCC cell lines (SCC-25, CAL-27, and Tca-8113) and clinical OSCC specimens. miR-18a over-expression markedly promoted human OSCC cell proliferation, invasion, migration in vitro . Bioinformatics analysis made a prediction that KLF4 was the candidate target gene of miR-18a, and western blotting confirmed the negative correlation between miR-18a and KLF4. Additionally, KLF4 was negatively associated with miR-18a in OSCC and abnormal expression of KLF4 attenuated miR-18a-mediated promotion in cell proliferation. In conclusmiR-18a p ion, remoted OSCC proliferation, migration and invasion abilities and suppressed the expression of, KLF4. This newly identified miR-18a/KLF4 axis may provide new insight into the pathogenesis and offers a potential target for OSCC therapy. Show more

Keywords: miR-18a, KLF4, OSCC, proliferation, metastasis, biomarker

DOI: 10.3233/CBM-181943

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-10, 2018

Authors: Liu, Longyang | Zeng, Zhaoyang | Yi, Juanjuan | Zuo, Liu | Lv, Jin | Yuan, Jianhuan | Lin, Zhongqiu | Luo, Rongcheng | Feng, Xin

Article Type: Research Article

Abstract: OBJECTIVES: To investigate TCF4 expression in epithelial ovarian cancer, and to explore its correlation with clinicopathological parameters and clinical prognosis of epithelial ovarian cancer. METHODS: From 2009 to 2017, 188 cases of paraffin-embedded epithelial ovarian cancer tissues and 41 paratumor ovarian tissues which had been confirmed at the memorial hospital of Sun Yat-sen University were collected in this study, and the expression of TCF4 was performed by immunohistochemistry using a polyclonal antibody specific for TCF4. RESULTS: The expression of TCF4 protein was associated with disease progression free survival and overall survival in epithelial …ovarian cancer patients; and TCF4 overexpression was associated with age, FIGO stage, lymph node metastasis, intraperitoneal metastasis, intestinal metastasis, vital status, intraperitoneal recurrence, and serum CA153. Moreover, in a multivariate Cox regression analysis TCF4 overexpression was an indeed independent prognostic factor in epithelial ovarian cancer. CONCLUSIONS: TCF4 may play an oncogenic role in epithelial ovarian cancer, and TCF4 is a useful independent prognostic biomarker of epithelial ovarian cancer, and it may provide a candidate target therapy treatment in future. Show more

Keywords: TCF4, ovarian cancer, expression, clinical significance

DOI: 10.3233/CBM-181849

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Yang, Ying | Zhang, Zongduan | Wu, Zhengzheng | Lin, Wei | Yu, Man

Article Type: Research Article

Abstract: BACKGROUND: Long noncoding RNA MIAT expression is related to the development of some diseases. However, the role of MIAT in melanoma was has seldom been studied. OBJECTIVE: To investigate the effect of the lncRNA MIAT on melanoma cells. METHOD: Microarray was used to analyze the lncRNAs expression in tissue samples. The expression of the lncRNA MIAT was detected by qRT-PCR. A CCK-8 assay was used to assess cell viability, and cell counting was used to analyze cell proliferation. Wound healing and Transwell invasion assays were used to detect the migration and invasion abilities, …respectively, of melanoma cells. Western blotting was performed to explore the molecular mechanisms of MIAT in melanoma. RESULTS: The lncRNA MIAT was overexpressed in melanoma. The overexpression of MIAT promoted cell proliferation, cell invasion and migration, while the knockdown of MIAT expression got the opposite results. MIAT significantly upregulated the phosphorylation of PI3K and AKT and promoted cMyc and cyclin D1 protein expression. CONCLUSION: LncRNA MIAT was a key factor to promote cell invasion, migration and proliferation through the PI3K/AKT signaling pathway. These findings may give us a potential way to treat melanoma. Show more

Keywords: lncRNA, MIAT, melanoma, migration, invasion, PI3K/AKT signaling pathway

DOI: 10.3233/CBM-181869

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Wakinoue, Shiro | Chano, Tokuhiro | Amano, Tsukuru | Isono, Takahiro | Kimura, Fuminori | Kushima, Ryoji | Murakami, Takashi

Article Type: Research Article

Abstract: BACKGROUND: Endometrioid ovarian carcinoma and clear cell ovarian carcinoma are both classified as endometriosis-associated ovarian cancer (EAOC). Despite the high rates of recurrence and mortality of EAOC, no prognostic biomarkers have been determined. ADP-ribosylation factor-like protein 4C (ARL4C) has been reported to be involved in various tumor progression processes, but its clinical significance for predicting prognosis in EAOC cases has never been studied. OBJECTIVE: The present study aimed to determine the clinical significance of ARL4C expression in EAOC prognosis. METHODS: ARL4C expression was semi-quantitatively evaluated via immunohistochemistry in 61 EAOC patients, and the …correlations between ARL4C expression and clinicopathological data and survival were statistically analyzed. RESULTS: Thirty-six (59%) cases had high levels of ARL4C, which was related to worse 5-year overall survival (OS) (log-rank test, p = 0.036). In multivariate Cox proportional hazard model, high ARL4C expression was a significantly independent predictive factor for worse 5-year OS (hazard ratio = 12.048, p = 0.0201) and 5-year PFS (hazard ratio = 8.130, p = 0.0036). CONCLUSIONS: ARL4C is a biomarker for worse prognosis and a novel therapeutic target in EAOC. Show more

Keywords: ADP-ribosylation factor-like protein 4C, endometriosis-associated ovarian cancer, clear cell ovarian carcinoma, endometrioid ovarian carcinoma

DOI: 10.3233/CBM-181836

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-7, 2018

Authors: Zhou, Zhijian | Ma, Jing

Article Type: Research Article

Abstract: MicroRNAs (miRNAs) have been demonstrated that play a critical role in tumorigenesis. The aim of this study is to identify the functional role of miR-378 in cholangiocarcinoma (CCA). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression levels of miR-378 in human CCA tissue samples and CCA cell lines. The receiver operating characteristic (ROC) curve was established, and the area under the ROC curve (AUC) was calculated to estimate the capacity of miR-378 in distinguishing CCA patients with different TNM stages. Kaplan-Meier survival analysis and Cox regression assay were performed to explore the prognostic value of miR-378. …Cell proliferation capacity was assessed by MTT assay. Cell migration and invasion were identified by Transwell assays. miR-378 was significantly elevated in CCA tissues when compared with adjacent normal tissues, and in CCA cell lines compared to HIBEC cells. And we found that the expression of miR-378 was significantly associated with TNM stage (P = 0.030) and lymph node metastasis (P = 0.018). ROC curve analysis result showed miR-378 could distinguish CCA patients with TNM stages III and IV from those with stages I and II, with the AUC was 0.816. Patients with high expression of miR-378 had a shorter overall survival rate (Log-rank P = 0.030). The miR-378 was proven to be an independent prognostic predictor for the CCA patients (HR = 1.735, 95% CI = 1.007–2.988, P = 0.041). Downregulation of miR-378 could inhibit cell proliferation, migration, and invasion. These results indicated that miR-378 function as an oncogene and promote CCA cells proliferation, migration, and invasion. The miR-378 could be a novel prognostic marker for CCA. Show more

Keywords: microRNA-378, cholangiocarcinoma, prognosis, proliferation, migration, invasion

DOI: 10.3233/CBM-181980

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-9, 2018

Authors: Zou, Ting | Wang, Ping Ling | Gao, Yan | Liang, Wen Tong

Article Type: Research Article

Abstract: Long noncoding RNAs (LncRNAs) are involved in the occurrence and progression of human tumors including ovarian cancer (OC). Long noncoding RNA HOTTIP has been found to be involved in several human tumors development. However, the role of HOTTIP in OC remains large unknown. In the present study, our results observed that lncRNA HOTTIP expression levels were notably higher in ovarian cancer tissue samples compared to adjacent normal tissue samples. Increased lncRNA HOTTIP expression levels were significantly associated with advanced FIGO stage and lymph node metastasis of ovarian cancer patients. Survival plots analysis results showed high lncRNA HOTTIP expression levels in …ovarian cancer patients showed a poor prognosis compared to patients with low lncRNA HOTTIP expression levels. Function assays showed that lncRNA HOTTIP knockdown in ovarian cancer cells decreased cell proliferation and cell invasion capacities. Furthermore, we demonstrated that inhibition of lncRNA HOTTIP suppressed Wnt/β -catenin signaling by downregulating β -catenin expression. Thus, these results suggest that aberrant HOTTIP expression level could serve as a promising biomarker for monitoring ovarian cancer and potential target of ovarian cancer treatment. Show more

Keywords: Ovarian cancer, long noncoding RNA, HOTTIP, prognosis, cell proliferation

DOI: 10.3233/CBM-181727

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-7, 2018

Authors: Ji, Xiaoyan | Zhu, Hanting | Dai, Xiaoxiao | Xi, Yujun | Sheng, Yujing | Gao, Ce | Liu, Hairui | Xue, Yanping | Liu, Jiachi | Shi, Jia | Zhang, Yongsheng | Chen, Yanming | Dai, Xingliang | Li, Ming | Wang, Aidong | Dong, Jun

Article Type: Research Article

Abstract: OBJECTIVE: Guanylate binding protein-1 (GBP1) is highly associated with cell proliferation, and can modulate growth and invasiveness of gliomas. The relationship between GBP1 expression and the prognosis of glioma patients is further evaluated for the purpose of investigating whether GBP1 can serve as an predictor for evaluating prognosis of glioma patients. METHODS: GBP1 expression in 528 glioblastoma multiforme (GBM) patients of The Cancer Genome Atlas (TCGA) database were investigated, then 103 surgical specimens from glioma patients in our center were further evaluated. The effect of GBP1 on proliferation, invasion and migration of glioma cells in vitro …was analyzed, and the effects of GBP1 on sensitivity of radiotherapy and chemotherapy on glioma cells in vitro were also analyzed. GBP1 associated signaling pathways were identified with Gene Set Enrichment Analysis (GSEA). Besides, the effect of GBP1 expression on proliferation of glioma cells in vivo was analyzed. RESULTS: In both TCGA database and our clinical data, GBM tissues exhibited increased mRNA expression of GBP1 gene, its expression level was co-related to PETN deletion and EGFR amplification, and was associated with prognosis of GBM patients. GBP1 overexpression can enhance migration and invasion ability of tumor cells in vitro , and in vivo studies showed that GBP1 can promote tumor proliferation, decrease survival in tumor-bearing mice. GSEA analysis predicted that GBP1 may play its biological roles via toll-like receptor pathway. CONCLUSION: This study provides new insights and evidences that high level expression of GBP1 is significantly correlated with progression and prognosis in GBMs. Furthermore, transfection of GBP1 revealed its regulation on migration and invasiveness of glioma cells, decreasing sensitivity of chemotherapeutic agent, shortening survival of tumor-bearing animals. These data demonstrate that GBP1 may serve as a novel prognostic biomarker and a potential therapeutic target for gliomas. Show more

Keywords: GBP1, glioblastoma mulfiforme, prognosis

DOI: 10.3233/CBM-171177

Citation: Cancer Biomarkers, vol. Pre-press, no. Pre-press, pp. 1-16, 2018