Cancer Biomarkers - Volume 17, issue 1

Authors: Zhou, Huangyan | Yuan, Min | Yu, Qiongfang | Zhou, Xiaoyan | Min, Weiping | Gao, Dian

Article Type: Review Article

Abstract: BACKGROUND: Autophagy is associated with the occurrence, development, cellular adaptation, progression, treatment and prognosis of gastric cancer (GC) and colorectal cancer (CRC). The effect of autophagy in these two cancers has attracted our attention. OBJECTIVE: The aim of this study was to describe the functional and regulatory mechanisms associated with autophagy in GC and CRC. METHODS: We reviewed recent publications describing the role of autophagy in GC and CRC, including the functional characteristics, clinical significance and regulatory mechanisms. RESULTS: Autophagy plays context-dependent dual roles in the development and progression of …GC and CRC. It can either promote tumor growth and cell survival or can contribute to tumor suppression and promote cell death. Both of these effects employ complex regulatory networks, such as those mediated by p53, PI3K/Akt/mTOR, Ras and microRNA. Among the cellular process associated with these pathways, autophagy is a potential target for anti-tumor therapy. CONCLUSION: Autophagy is associated with both tumorigenic and protective effects in cancer. However, the role of autophagy in GC and CRC remains unclear. Although the translation of the basic science of autophagy into clinical practice is a long process, the modulation of autophagy as a potential therapeutic approach in GC and CRC merits further investigation. Show more

Keywords: Autophagy, gastric cancer, colorectal cancer

DOI: 10.3233/CBM-160613

Citation: Cancer Biomarkers, vol. 17, no. 1, pp. 1-10, 2016

Authors: Xu, Jia-Ning | Shen, Dong | Mao, Wei-Dong | Lin, Qing-Fen | Lin, Feng | Lu, Chao

Article Type: Research Article

Abstract: Breast cancer is currently the most common malignancy affecting women worldwide. It had been shown that the allopregnanolone biosynthesis was associated with tumorigenesis and PK11195, the Translocator Protein 18 KDa (TSPO) antagonist, had the effects of the allopregnanolone biosynthesis. However, little is known about the association between the effects of PK11195 on the breast cancer and the allopregnanolone biosynthesis. To evaluate this, the breast cancer cell lines MCF-7 and T47D were cultured. Cell viability and proliferation were determined by CCK-8 assay. The IC50 of PK11195 on the MCF-7 and T47D were 5.4 nM and 6 nM. The cell viability and …proliferation of AC-5216 (TSPO selective ligand, 3 and 6 nM) was blocked by PK11195 (5.4 nM and 6 nM). Moreover, we evaluated the role of allopregnanolone biosynthesis in the effects of TSPO on breast cancer. Enzyme-Linked ImmunoSorbent Assay (ELISA) was used in the measurement of the allopregnanolone level. We found that the allopregnanolone level was increased by AC-5216 (3 and 6 nM) and the increase was reversed by PK11195 (5.4 nM and 6 nM, resepectively) in MCF-7 and T47D. The TSPO mRNA level was determined by real time polymerase chain reaction (PCR). The TSPO mRNA level were increased by AC-5216 (6 nM), which the increases were reversed by PK11195 (5.4 nM and 6 nM, resepectively) in MCF-7 and T47D. Collectedly, it firstly indicated that the effects of PK11195 on MCF-7 and T47D were associated with the decrease of allopregnanolone biosynthesis, which was mediated by TSPO. Show more

Keywords: AC-5216, allopregnanolone, MCF-7, T47D, PK11195, TSPO

DOI: 10.3233/CBM-160610

Citation: Cancer Biomarkers, vol. 17, no. 1, pp. 11-16, 2016

Authors: Kargı, Ayşegül | Demirpençe, Özlem | Gündüz, Şeyda | Göktaş, Sevil | Alikanoǧlu, Arsenal Sezgin | Yıldırım, Mustafa

Article Type: Research Article

Abstract: RCC constitutes approximately 90% of all renal malignancies and 2-3% of all malignant tumours in adults. In spite of the improvement in radiologic methods, nearly 30% of the early metastatic RCC patients are incidentally diagnosed. HMGB1 is an extracellular signalling molecule that plays a role both in inflammation and carcinogenesis. Patients who were followed in Medical Oncology Departments of Denizli Government Hospital and Antalya Education and Research Hospital with a histopathological diagnosis of RCC between years 2010-2012 were enrolled in this study. HMGB1 levels were also assessed in a manually performed quantitative sandwich-enzyme-linked immunosorbent assay (ELISA) assay kit. In our …study, we showed that the serum level of HMGB1, whether 149.9 pg/ml or not is important in differential diagnosis between patient and control group. Show more

Keywords: Renal cell cancer, diagnosis, high mobility group box (HMGB) proteins, Elisa

DOI: 10.3233/CBM-160611

Citation: Cancer Biomarkers, vol. 17, no. 1, pp. 17-20, 2016

Authors: Kobayashi, Sumiko | Ueda, Yasunori | Nannya, Yasuhito | Shibayama, Hirohiko | Tamura, Hideto | Ogata, Kiyoyuki | Akatsuka, Yoshiki | Usuki, Kensuke | Ito, Yoshikazu | Okada, Masaya | Suzuki, Takahiro | Hata, Tomoko | Matsuda, Akira | Tohyama, Kaoru | Kakumoto, Keiji | Koga, Daisuke | Mitani, Kinuko | Naoe, Tomoki | Sugiyama, Haruo | Takaku, Fumimaro

Article Type: Research Article

Abstract: BACKGROUND: This present study was designed to follow up 82 patients among 115 MDS patients registered in study ODK-0801 for 5 years, to analyze the relationship between the WT1 mRNA expression level and prognosis. OBJECTIVE: This study aimed to investigate the clinical utility of WT1 mRNA expression levels. METHODS: After study ODK-0801, we investigated the conditions of the same patients once a year, including any clinical and laboratory findings supporting the diagnosis, and treatment among the living patients. RESULTS: When we assessed the survival time of 82 MDS patients by …WT1 mRNA expression level, there were significant differences between the < 500 and ≥ 104 copies/μ g RNA groups and between the 500-104 and ≥ 104 copies/μ g RNA groups for BM levels (p < 0.01). Examination of the time of freedom from acute myeloid eukemia (AML) transformation indicated that a high WT1 mRNA expression level (> 104 copies/μ g RNA) was a strong prognostic factor for a short time to AML transformation. CONCLUSION: The results indicate that the tumorigenesis of MDS is likely to originate at the stem cell level, suggesting that the WT1 mRNA level measurement in the BM is an effective prognostic marker in patients with MDS. Show more

Keywords: Myelodysplastic syndromes, follow-up study, Wilms tumor 1 mRNA expression level, peripheral blood, bone marrow, IPSS, WPSS, IPSS-R

DOI: 10.3233/CBM-160612

Citation: Cancer Biomarkers, vol. 17, no. 1, pp. 21-32, 2016

Authors: Miao, Yi | Yan, Qin | Li, Shuangdi | Li, Bilan | Feng, Youji

Article Type: Research Article

Abstract: The aim of present study was to investigate the role of preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) used as prognostic markers for predicting chemotherapeutic response and survival outcomes in patients with epithelial ovarian cancer (EOC) who are receiving platinum-based chemotherapy. A total of 344 patients diagnosed with EOC who are receiving platinum-based chemotherapy from 2005 to 2010 in the hospital were enrolled. NLR and PLR were calculated from complete blood cell count taken before operation. The patients were divided into platinum-resistant (P-R) group and platinum-sensitive (P-S) group according to chemotherapeutic response. Clinicopathologic variables and …outcomes were retrospectively collected and compared among groups. We used receiver operating characteristic (ROC) curves to calculate optimal cut-off values for NLR and PLR to predict chemotherapeutic response and prognosis. The AUC, sensitivity, specificity of NLR > 3.02 to predict platinum resistance were 0.819, 75.0% and 81.45%, respectively. The corresponding values of PLR > 207 were 0.727, 60.42% and 85.48%, respectively. Patients with lower value of NLR (NLR < 3.02) or PLR (PLR < 207) had a longer progression-free survival (PFS) and overall survival (OS). In multivariate analysis, NLR and PLR showed a significant association with PFS (hazard ratio [HR], 1.733; 95%CI, 1.225-2.453, P = 0.002 and HR, 1.952; 95%CI, 1.430-2.662, P < 0.001) and OS (HR, 1.616; 95%CI, 1.138-2.297, P = 0.007, and HR, 2.167; 95%CI, 1.565-3.000, P < 0.001). These results suggest that the assessment of NLR and PLR could assist the identification of patients with poor prognosis and had potential clinical value in predicting platinum resistance in patients with EOC. Show more

Keywords: Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, epithelial ovarian cancer, platinum resistance, prognosis

DOI: 10.3233/CBM-160614

Citation: Cancer Biomarkers, vol. 17, no. 1, pp. 33-40, 2016

Authors: Lv, Cai | Huang, Yuan | Liu, Zhen-Xiang | Yu, Dan | Bai, Zhi-Ming

Article Type: Research Article

Abstract: Salidroside has been reported to exhibit anticancer properties. This study aimed to investigate the effects of salidroside on renal cell carcinoma growth. Cell viability and proliferation was assessed by Cell Counting Kit-8 and colony formation assays in A498 and 786-0 cells. The effects of salidroside on in vivo tumor growth were also assessed in a mouse xenograft model of renal cell carcinoma. Flow cytometry was used to analyze cell cycle and apoptosis and protein levels were determined by western blotting. Salidroside reduced cell viability and colony formation in both cell lines in a concentration- and time-dependent manner. Tumor growth …was also suppressed in the mouse model. Furthermore, salidroside induced significant G1 phase cell cycle arrest and induced apoptosis in both A498 and 786-0 cells. Higher concentrations of salidroside reduced the levels of phosphorylated signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2). These results suggested that salidroside produced potent anticancer properties in renal cell carcinoma by modulating JAK2/STAT3 signaling. Administration of salidroside to patients with renal cell carcinoma might provide a promising therapeutic strategy for this malignancy. Show more

Keywords: Salidroside, renal cell carcinoma, growth, JAK2/STAT3, apoptosis

DOI: 10.3233/CBM-160615

Citation: Cancer Biomarkers, vol. 17, no. 1, pp. 41-47, 2016

Authors: Qu, Jianjun | Qu, Xiangyang

Article Type: Research Article

Abstract: BACKGROUND: Chemotherapy-sensitivity test is crucial to screen out patients who are insensitive to the treatment and to avoid unnecessary preoperative chemotherapy. OBJECTIVE: To investigate the predictors for the response to mFOLFOX7 neoadjuvant chemotherapy (NACT) in advanced gastric cancer. METHODS: The expression of C-met, EGFR, HER2, Ki-67, MMP7, P53 and TOPOII in tumor tissue from 53 locally advanced gastric cancer patients (AGC) was detected by immunohistochemistry. The relationship between tumor marker expression and the efficacy of NACT was determined by chi-square test and multivariate logistic regression analysis. The relationship between the combined expression of …HER2 and P53 and the efficacy of NACT was further analyzed by chi-square test. RESULTS: The overall response rate was 52.8% (28/53). There were no significant differences of tumor markers' expression before and after chemotherapy (P> 0.05). The response rate in HER2-positive patients (83.33%) was significantly higher than that in HER2-negative patients (43.90%, P= 0.016), whereas the response rate in P53-positive patients (35.71%) was significantly lower than that in P53-negative patients (72.0%, P= 0.008). Moreover, the response rate was the highest in the patients who were positive for HER2 but negative for P53. CONCLUSION: HER2 and P53 were identified as independent predictors for the response to mFOLFOX7 NACT in AGC. Show more

Keywords: Gastric cancer, neoadjuvant chemotherapy, predictors

DOI: 10.3233/CBM-160616

Citation: Cancer Biomarkers, vol. 17, no. 1, pp. 49-54, 2016

Authors: Rychlíková, Jana | Vecka, Marek | Jáchymová, Marie | Macášek, Jaroslav | Hrabák, Petr | Zeman, Miroslav | Vávrová, Lucie | Řoupal, Jan | Krechler, Tomáš | ák, Aleš

Article Type: Research Article

Abstract: INTRODUCTION: We analyzed concentrations of osteopontin (OPN) in patients with pancreatic ductal adenocarcinoma (PDAC) in order to determine firstly whether it is useful to distinguish between PDAC patients and those with chronic non-hereditary pancreatitis (CP) and type 2 diabetes mellitus (T2DM), and secondly whether OPN concentrations depend on the PDAC stage. METHODS: Groups consisting of 64 patients with PDAC, 71 with CP, 67 with T2DM and 48 healthy controls (CON) were enrolled in the study. Controls were compared with regard to levels of OPN, oxidative stress markers, conventional tumor markers and other biochemical parameters. …RESULTS: Levels of OPN were higher in patients with PDAC compared with CP patients (P< 0.001), T2DM (P< 0.001) and CON (P< 0.001). There were increased OPN levels in CP patients in comparison with T2DM (P< 0.001) and CON (P< 0.001). Patients with PDAC in stage IV had higher OPN levels than PDAC patients in stage III (P< 0.01). There was no difference in OPN levels of PDAC patients in stage III compared to patients in stage II. CONCLUSION: Our pilot study demonstrates the usefulness of estimating OPN levels to differentiate between pancreatic cancer and chronic pancreatitis. Higher OPN levels over 102 ng/ml could be a potential diagnostic biomarker for pancreatic cancer. Show more

Keywords: Osteopontin, pancreatic ductal adenocarcinoma, chronic non-hereditary pancreatitis, type 2 diabetes mellitus

DOI: 10.3233/CBM-160617

Citation: Cancer Biomarkers, vol. 17, no. 1, pp. 55-65, 2016

Authors: Ben Ayed-Guerfali, Dorra | Charfi, Slim | Khabir, Abdelmajid | Sellami-Boudawara, Tahia | Gargouri, Ali | Mokdad-Gargouri, Raja

Article Type: Research Article

Abstract: BACKGROUND: Inflammation and hormonal signalling induce the cyclooxygenase-2 (COX-2) expression in various human cancers including Gastric Cancer (GC). GC remains among the human malignancies diagnosticated at advanced tumor stage and thus having a poor prognosis. COX-2 is a key protein in cancer progression which is involved in proliferation, invasion, and metastasis of tumor cells. OBJECTIVE: The aim of this study was to investigate the expression of COX-2 and its association with clinico-patholocigal parameters and survival in Tunisian GC patients and to correlate COX-2 expression with others cancer-related proteins. METHODS: The immunohistochemistry was …used to study the expression of COX-2 on 93 patients with gastric adenocarcinoma. RESULTS: Our results show that COX-2 immunostaining is negative to weak in 51.6%, moderate in 33.3%, and intense in 15.1% of tumor tissues. The expression of COX-2 associated significantly with tumor differentiation (p = 0.003), and histological type (p = 0.039). Furthermore, lack of COX-2 expression is significantly associated with 1-year (p= 0.005), 2-years (p= 0.000), and 5-years (p= 0.042) relapse free survival. In addition, Cox regression model, revealed that metastasis (p= 0.014), tumor site (p= 0.013), histotype (p = 0.02), and COX-2 expression (p = 0.003) are independent factors for prognosis. Regarding the relationship between COX-2 and cancer related proteins, we found that COX-2 expression is positively associated with APC (p = 0.006), and P53 (p = 0.026), supporting a cross link between these proteins in gastric carcinogenesis. CONCLUSION: Our findings emphasize the importance of COX-2 as a potential marker of tumor progression and prognosis in GC, and that the inhibition of COX-2 activity may have a therapeutic benefit in GC. Show more

Keywords: COX-2, gastric carcinoma, prognosis, immunohistochemistry

DOI: 10.3233/CBM-160618

Citation: Cancer Biomarkers, vol. 17, no. 1, pp. 67-73, 2016

Authors: Li, Liang-Qing | Yang, Yang | Chen, Hui | Zhang, Lin | Pan, Dun | Xie, Wen-Jun

Article Type: Research Article

Abstract: Cancer cells usually utilize glucose as a carbon source for aerobic glycolysis, which is named as ``Warburg effect''. Recent studies have shown that MicroRNAs (miRNAs), a class of short and non-coding RNAs, play a role in the regulation of metabolic reprograming in cancer cells. In the present study, we report that miR-181b negatively regulates glycolysis in gastric cancer cells. Over-expression of miR-181b mimics reduces the glucose uptake and lactate production, while increasing the cellular ATP levels in NCI-N87 and MGC80-3 cells. At the molecular level, miR-181b directly inhibits the expression level of hexokinase 2 (HK2), a key enzyme that …catalyzes the first step of glycolysis, through targeting its 3'-untranslated region. In addition, miR-181b represses cell proliferation and migration and is dramatically down-regulated in human gastric cancers. Therefore, our data disclose a novel function of miR-181b in reprogramming the metabolic process in gastric cancer. Show more

Keywords: MicroRNA-181b, glycolysis, gastric cancer, hexokinase 2

DOI: 10.3233/CBM-160619

Citation: Cancer Biomarkers, vol. 17, no. 1, pp. 75-81, 2016

Authors: Koch, Michael O. | Cho, Jane S. | Kaimakliotis, Hristos Z. | Cheng, Liang | Sangale, Zaina | Brawer, Michael | Welbourn, William | Reid, Julia | Stone, Steven

Article Type: Research Article

Abstract: BACKGROUND: Determining the optimal treatment for biochemical recurrence (BCR) after radical prostatectomy (RP) is challenging. OBJECTIVE: We evaluated the ability of CCP score (a prognostic RNA expression signature) to discriminate between systemic disease and local recurrence in patients with BCR after RP. METHODS: Sixty patients with BCR after RP were selected for analysis based on: 1) metastatic disease, 2) non-response to salvage external beam radiotherapy (EBRT), and 3) durable response to salvage EBRT. CCP scores were generated from the RNA expression of 46 genes. Logistic regression assessed the association between CCP score and …patient group. RESULTS: Passing CCP scores were generated for 47 patients with complete clinical and pathologic data. CCP score predicted clinical status when comparing patients with metastatic disease or non-responders to salvage therapy to patients with durable response (p = 0.006). CCP score remained significantly predictive of clinical status after accounting for time to BCR, PSA level at BCR, and Gleason score (p = 0.0031). CONCLUSIONS: Elevated CCP score was associated with increased risk of systemic disease, indicating that CCP score may be useful in identifying patients with BCR who are most likely to benefit from salvage radiation therapy. Show more

Keywords: Prostate cancer, prostatectomy, cell cycle progression score, biochemical recurrence, salvage radiotherapy

DOI: 10.3233/CBM-160620

Citation: Cancer Biomarkers, vol. 17, no. 1, pp. 83-88, 2016

Authors: Chen, You-Fang | Li, Qiang | Chen, Dong-Tai | Pan, Jia-Hao | Chen, Yong-Hua | Wen, Zhe-Sheng | Zeng, Wei-An

Article Type: Research Article

Abstract: BACKGROUND: The serum uric acid (SUA) is the end-product from the metabolic breakdown of purine nucleotides. It has been considered to be a prognostic factor for malignant tumor in several researches. However, its prognostic value in patients with esophageal squamous cell carcinoma (ESCC) has not been elucidated. METHODS: We retrospectively reviewed the records of 209 ESCC patients who underwent R0 esophagectomy. A receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value for pre-operative SUA levels and to divide the ESCC patients into two groups. Furthermore, we analyzed the pre-operative serum uric …acid (SUA) levels and its relationship with the clinicopathological parameters and the prognosis of 209 ESCC patients. RESULTS: Optimal cut-off value for pre-operative SUA in ROC analysis was 304.5 μ mol/l (sensitivity 67.46%, specificity 65.06%). SUA low- or high-levels were associated with gender (P< 0.001), smoking status (P< 0.001), pN statues (P= 0.003) and TNM stage (P= 0.010). SUA levels, tumor differentiation and pTNM stage were independent predictors of ESCC patient survival in a multivariate analysis. CONCLUSIONS: The pre-operative level of SUA is an independent prognostic predictor in ESCC patients who undergo R0 esophagectomy and patients with higher SUA level may have an unfavorable survival probability. Show more

Keywords: Esophageal squamous cell carcinoma, SUA, overall survival, disease-free survival, prognostic factor

DOI: 10.3233/CBM-160621

Citation: Cancer Biomarkers, vol. 17, no. 1, pp. 89-96, 2016

Authors: Halkova, Tereza | Dvorakova, Sarka | Sykorova, Vlasta | Vaclavikova, Eliska | Vcelak, Josef | Vlcek, Petr | Sykorova, Pavla | Kodetova, Daniela | Betka, Jan | Lastuvka, Petr | Bavor, Petr | Hoch, Jiri | Katra, Rami | Bendlova, Bela

Article Type: Research Article

Abstract: BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. In addition to causal somatic mutations in the BRAF gene and RET/PTC rearrangements, the contribution of single nucleotide polymorphisms (SNPs) in low-penetrance genes in the development of PTC has been proposed. METHODS: Four SNPs in the XRCC1 (Arg399Gln, Arg280His, Arg194Trp and T-77C) and one SNP from each of three other genes participating in DNA repair pathways and/or cell cycle regulation (ATM Asp1853Asn, TP53 Arg72Pro, CDKN1B Val109Gly) were selected. The allelic and genotypic distributions of these variants as …well as haplotypes of the XRCC1 were examined in 583 individuals comprising well-characterized cohorts of 209 PTC patients and 374 healthy volunteers. Correlations of polymorphism with clinical-pathological data and mutation status were performed. RESULTS: XRCC1 T-77C polymorphism affects the genetic susceptibility for PTC development in men, the specific combination of XRCC1 haplotypes correlates with RET/PTC incidence, CDKN1B Val109Gly significantly influences the risk of developing PTC regardless of gender and in PTC cases, selected genotypes of TP53 Arg72Pro and ATM Asp1853Asn were significantly associated with monitored tumour characteristics. CONCLUSION: It seems that SNPs in studied regulating genes contribute to the development of PTC and modify the tumour behaviour or characteristics. Show more

Keywords: Papillary thyroid cancer, molecular genetics, SNP, DNA repair, cell cycle regulator

DOI: 10.3233/CBM-160622

Citation: Cancer Biomarkers, vol. 17, no. 1, pp. 97-106, 2016

Authors: Zambo, Iva | Hermanova, Marketa | Zapletalova, Danica | Skoda, Jan | Mudry, Peter | Kyr, Michal | Zitterbart, Karel | Sterba, Jaroslav | Veselska, Renata

Article Type: Research Article

Abstract: BACKGROUND: Nestin, CD133 and ABCG2 are recently discussed as putative markers, co-expression of which might determine a cancer stem cell (CSC) phenotype in sarcomas. OBJECTIVE: Our study is focused on immunohistochemical analysis of nestin, CD133 and ABCG2 expression in rhabdomyosarcoma, Ewing sarcoma and osteosarcoma. Furthermore, we also analyzed the possible correlation of nestin, CD133 and ABCG2 expression levels with the patient outcome to identify potential prognostic values of these three putative CSC markers in the same cohorts. METHODS: Using immunohistochemistry, expression of nestin, CD133 and ABCG2 was analyzed in 24 rhabdomyosarcoma, 22 Ewing …sarcoma and 10 osteosarcoma tissue samples and expression levels of these markers were correlated with clinical outcome. RESULTS: High nestin levels indicate poor prognosis in patients with Ewing sarcoma (P = 0.001), and high CD133 expression is associated with shorter survival in rhabdomyosarcoma patients (P = 0.002). In contrast, no significant relationship was found between ABCG2 expression and the clinical outcome. CONCLUSIONS: Our analysis represents the first complex study of these three putative CSCs markers together in three different types of pediatric sarcomas and showed their possible prognostic values in these tumors. Show more

Keywords: Rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, cancer stem cell markers, prognosis

DOI: 10.3233/CBM-160623

Citation: Cancer Biomarkers, vol. 17, no. 1, pp. 107-116, 2016