Cancer Biomarkers - Volume 16, issue 1

Authors: Wang, Qi | Wang, Shuai | Sun, Si-Qiao | Cheng, Zhi-Hua | Zhang, Yang | Chen, Guang | Gu, Meng | Yao, Hai-Jun | Wang, Zhong | Zhou, Juan | Peng, Yu-Bing | Xu, Ming-Xi | Zhang, Ke | Sun, Xi-Wei

Article Type: Research Article

Abstract: OBJECTIVE: This study was to explore the effects of RNA interference mediated vascular endothelial growth factor (VEGF ) gene silencing on biological behavior of renal cell carcinoma (RCC), transplanted renal tumor and angiogenesis in nude mice. METHODS: The specific siRNA sequence targeting VEGF were designed and synthesized to construct hVEGF-siRNA plasmid which was transfected into RCC 786-O cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the detection of VEGF gene expression and western blot was adopted for the examination of VEGF protein expression. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell …growth as well as cell migration and invasion. The transplanted renal tumor models in nude mice were established, and the growth condition of nude mice, and VEGF protein expression in transplanted tumor slices and the microvessel density (MVD) were detected. RESULTS: The expression level of VEGF mRNA in VEGF-siRNA group was significant lower than that in the control group and negative group, suggesting that establishment of plasmid specifically inhibited the expression of VEGF gene The expression level of VEGF protein in VEGF-siRNA group was significant lower than that in the control group and negative group. VEGF gene silencing has the significant inhibition effects on proliferation, migration and invasion of RCC 786-O cells. The tumor weight, VEGF protein positive rate and MVD in VEGF-siRNA group were significant lower than those in negative group and blank group. CONCLUSION: The VEGF gene silencing could inhibit the cell proliferation, migration and invasion of RCC 786-O cells; inhibition of VEGF protein expression could prevent transplanted RCC growth and tumor angiogenesis. Show more

Keywords: Vascular endothelial growth factor, renal cell carcinoma, transplanted tumor, nude mice, gene silencing, biological behavior, angiogenesis, gene therapy

DOI: 10.3233/CBM-150535

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 1-9, 2016

Authors: Li, Xiao | Gao, Yang | Zhou, Hai | Xu, Weizhang | Li, Pu | Zhou, Jin | Xu, Ting | Yu, Bin | Xu, Zicheng | Zou, Qing | Yin, Changjun | Cai, Hongzhou | Shen, Wenyi

Article Type: Research Article

Abstract: OBJECTIVE: A functional -94 insertion/deletion polymorphism (rs28362491) in the promoter of the NF-κ B1 gene was reported to influence NF-κ B1 expression and confer susceptibility to different types of cancer. This study aims to determine whether the polymorphism is associated with the risk of urinary cancer, including renal cancer, bladder cancer and prostate cancer. METHODS: TaqMan method was applied to genotype the NF-κ B1 -94 ins/del ATTG promoter polymorphism in three case-control studies: renal cell carcinoma group (1216 cases and 1588 controls), bladder cancer group (730 cases and 780 controls), and prostate cancer group (820 cases …and 945 controls). Logistic regression was used to assess the association between the polymorphism and urinary cancer risk. RESULTS: The del/del genotype was detected to be associated with a statistically significant increased risk of bladder cancer when taking the ins/ins genotypes as reference (P < 0.001, adjusted odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.14-1.52). Furthermore, in bladder cancer, the same results were observed in the del/del genotype compared with the ins/ins + ins/del genotypes (P < 0.001, OR = 1.82, 95% CI = 1.41-2.35), and the del allele compared with the ins allele (P < 0.001, OR = 1.29, 95% CI = 1.12-1.49). However, no significant difference was observed in the associations between the NF-κ B1 polymorphism and the risk of renal cell carcinoma or prostate cancer in all kinds of models. CONCLUSIONS: In the Chinese population, the -94 ins/del ATTG polymorphism in NF-κ B1 promoter may contribute to the etiology of bladder cancer instead of renal cell carcinoma or prostate cancer. Show more

Keywords: NF-κ B1 gene, polymorphism, renal cell carcinoma, bladder cancer, prostate cancer

DOI: 10.3233/CBM-150536

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

Authors: Luo, Yung-Hung | Tseng, Pei-Chun | Lee, Yu-Chin | Perng, Reury-Perng | Whang-Peng, Jacqueline | Chen, Yuh-Min

Article Type: Research Article

Abstract: BACKGROUND: The use of liquid tissue, such as circulating cells, to predict treatment response is attracting more attention. OBJECTIVE: The aim of this study was to evaluate association between circulating markers and treatment response. METHODS: One hundred and twelve advanced pulmonary adenocarcinoma patients who were going to receive epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were included. Tumor tissue and plasma specimens were collected before treatment and analyzed for EGFR mutation and plasma IL-6 and IL-8. Pre-treatment peripheral blood CD146+/CD3- cells (as circulating endothelial cells, CECs), CD34+/CD45- cells (as endothelial progenitor cells, …EPCs), and CD133+ cells (as cancer stem cells, CSCs) were measured with flow cytometry. RESULTS: The progression-free survival (PFS) was significantly longer in patients with low CEC, low EPC, and low CSC counts than in those with high cell counts (p < 0.001, 0.041, and 0.001, respectively). Multivariate analysis showed that mutant plasma EGFR (pEGFR) was a poor prognostic factor in EGFR -mutated patients (p = 0.048), and there was a tendency for EGFR mutation-negative patients with high IL-6 level to have worse overall survival (p = 0.051). CONCLUSIONS: CECs, EPCs, CSCs, and mutant pEGFR are useful predictive biomarkers of EGFR-TKI treatment efficacy. IL-6 may predict prognosis in advanced lung cancer. Show more

Keywords: Adenocarcinoma, cancer stem cells, circulating endothelial cells, endothelial progenitor cells, epidermal growth factor receptor (EGFR), cytokines

DOI: 10.3233/CBM-150537

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 19-29, 2016

Authors: Najafi, Ali | Tavallaei, Mahmood | Hosseini, Sayed Mostafa

Article Type: Research Article

Abstract: Non-small cell lung cancers (NSCLCs) is a prevalent and heterogeneous subtype of lung cancer accounting for 85 percent of patients. MicroRNAs (miRNAs), a class of small endogenous non-coding RNAs, incorporate into regulation of gene expression post-transcriptionally. Therefore, deregulation of miRNAs' expression has provided further layers of complexity to the molecular etiology and pathogenesis of different diseases and malignancies. Although, until now considerable number of studies has been carried out to illuminate this complexity in NSCLC, they have remained less effective in their goal due to lack of a holistic and integrative systems biology approach which considers all natural elaborations of …miRNAs' function. It is able to reliably nominate most affected signaling pathways and therapeutic target genes by deregulated miRNAs during a particular pathological condition. Herein, we utilized a holistic systems biology approach, based on appropriate re-analyses of microarray datasets followed by reliable data filtering, to analyze integrative and combinatorial deregulated miRNA-mRNA interaction network in NSCLC, aiming to ascertain miRNA-dysregulated signaling pathway and potential therapeutic miRNAs and mRNAs which represent a lion' share during various aspects of NSCLC's pathogenesis. Our systems biology approach introduced and nominated 1) important deregulated miRNAs in NSCLCs compared with normal tissue 2) significant and confident deregulated mRNAs which were anti-correlatively targeted by deregulated miRNA in NSCLCs and 3) dysregulated signaling pathways in association with deregulated miRNA-mRNAs interactions in NSCLCs. These results introduce possible mechanism of function of deregulated miRNAs and mRNAs in NSCLC that could be used as potential therapeutic targets. Show more

Keywords: Lung cancer, microRNAs, signaling pathway, systems biology

DOI: 10.3233/CBM-150538

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 31-45, 2016

Authors: Araújo, Amanda Souza | Nogueira, Ingrid Correia | Neto, Antero Gomes | de Medeiros, Israel Lopes | Morano, Maria Tereza Aguiar Pessoa | da Silva, Guilherme Pinheiro Ferreira | Santos, Flávia Almeida | Filho, Manoel Odorico De Moraes | Pereira, Eanes Delgado Barros

Article Type: Research Article

Abstract: BACKGROUND: Major thoracic surgery is characterized by release of inflammatory markers.The objective of this study was to assess the preoperative and postoperative systemic inflammatory markers of patients undergoing lung cancer resection. METHODS: This is a prospective follow up study conducted with 48 patients submitted to lung cancer resection.All patients were assessed before and 1 month after surgery through measurement of fibrinogen and C-reative protein(CRP), pulmonary function tests, 6- minute Walk Test (6MWT), maximal inspiratory pressure (PImax) and maximal expiratory preasure (PEmax), anxiety and depression scale and karnofsky performance status scale. RESULTS: Both fibrinogen …and CRP were higher 1 month after surgery, although only the change in CRP was statistically significant (p= 0.03). The following functional parameters: 6MWT, PImax, PEmax, FEV1(%) and FVC(%) decreased after surgery with p≤ 0.001 for all the parameters. Anxiety and depression improved and Karnofsky decrease after surgery (p= 0.03, p= 0.01 and p= 0.02; respectively). Change in CRP score following lung resection correlated significantly with changes in fibrinogen (r= 0.40; p= 0.003), change in Karnofsky scale (r= -0.50; p< 0.001) and a borderline significant trend with the 6MWT (r= -0.28; p= 0.05). With the exception of video-assisted thoracoscopic surgery (VATS), who had a significantly lower fibrinogen level 1 month after surgery compared with thoracotomy (p= 0.01), no significant differences in fibrinogen or CRP were noted in other subgroups of patients considered at increased risk for higher levels of inflammation compared with lower risk counterparts. CONCLUSION: Lung cancer resection surgery was associated with increased level of CRP, 1 month after surgery, and correlated directly with change in fibrinogen and inversely with measurement of performance status. VATS provided lower level of fibrinogen after surgery. Show more

Keywords: Lung cancer, surgery, inflammatory mediators

DOI: 10.3233/CBM-150539

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 47-53, 2016

Authors: Lamperska, Katarzyna M. | Kozlowski, Piotr | Kolenda, Tomasz | Teresiak, Anna | Blizniak, Renata | Przybyla, Weronika | Masternak, Michal M. | Golusinski, Pawel | Golusinski, Wojciech

Article Type: Research Article

Abstract: BACKGROUND: The necessity of prediction and treatment outcome improvement of HNSCC needs to find new biomarkers. miRNAs seem to be good candidate for that. OBJECTIVE: Analysis of selected 5 miRNAs (let-7d, miR-18a, miR-21, miR-205 and miR-375) as potential biomarkers that allows to distinguish tumor and healthy tissue taken from HNSCC patients. METHODS: Tumor and normal epithelial tissues were obtained from 75 HNSCC patients to analyze selected miRNAs. RESULTS: Analysis indicated significant increase of miR-21 and miR-205 in tumor when compared with healthy tissue (p= 0.0069 and p= 0.0029, respectively). There …was a significant correlation between let-7d and miR-18a. let-7d was down-regulated in 34.67% cases, miR-18a in 29.33%, miR-21 in 20%, miR-205 in 30.67% and miR-375 in 52% cases. At the same time over-expression of let-7d was detected in 18.67% cases, miR-18a in 22.67%, miR-21 in 48%, miR-205 in 41.33% and miR-375 in 52% cases. There was no correlation between miRNA expression and clinical data and the course of illness. CONCLUSION: Our study indicated that miR-21 and miR-205 can be used to analyze the clarity of surgical margins and that concomitant changes in the expression of let-7 and miR-18a in tumor tissues might represent important future markers indicating the biology of HNSCC. These observations will help with developing personalization for HNSCC patients' treatment. Show more

Keywords: Cancer, HNSCC, miRNA profile, qRT-PCR, biomarker

DOI: 10.3233/CBM-150540

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 55-64, 2016

Authors: Gao, Zhuo-Wei | Huang, Jing-Bin | Lin, Qing | Qin, Qiang | Liang, Yao-Jun | Zhou, Lu | Luo, Min

Article Type: Research Article

Abstract: Meningioma is one of the common brain tumors in adults. 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 meningioma and the allopregnanolone biosynthesis. To evaluate this, the meningioma cell line IOMM-LEE was applied. Cell viability and proliferation were determined by CCK-8 assay. The IC50 of PK11195 on the IOMM-LEE was 1.505 ± 0.08 nM. The cell viability and proliferation of AC-5216 (TSPO selective ligand, 2 and 4 …nM) was blocked by PK11195 (1.5 nM). Further, we evaluated the role of allopregnanolone biosynthesis in the effects of TSPO on meningioma. Enzyme-Linked ImmunoSorbent Assay (ELISA) was used in the measurement of the allopregnanolone level. It showed that the allopregnanolone level was increased by AC-5216 (2 and 4 nM) and the increase was reversed by PK11195 (1.5 nM). Collectedly, it firstly indicated that the effects of PK11195 on meningioma were relevant to the decrease of allopregnanolone biosynthesis, which was mediated by TSPO. Show more

Keywords: AC-5216, allopregnanolone, meningioma, PK11195, TSPO

DOI: 10.3233/CBM-150541

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 65-69, 2016

Authors: Wang, Yihan | Peng, Qian | Jia, Hongyuan | Du, Xiao

Article Type: Research Article

Abstract: BACKGROUND: The Hedgehog (Hh) signaling pathway has recently been reported to be associated with the prognosis of digestive system cancers. However, the results are inconsistent. OBJECTIVE: This study aimed to investigate the association between Hh pathway components and survival outcomes in patients with digestive system cancers. METHODS: We conducted a comprehensive retrieval in PubMed, EMBASE and Cochrane library for relevant literatures until May 1st, 2015. The pooled hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) with 95% confidence intervals (CIs) were calculated to clarify the prognostic value of Hh pathway …components, including Shh, Gli1, Gli2, Smo and Ptch1. RESULTS: A total of 16 eligible articles with 3222 patients were included in the meta-analysis. Pooled HR suggested that over-expression of Shh and Gli1 were both associated with poor OS (HR = 1.87, 95% CI: 1.14-3.07 and HR = 1.96, 95% CI: 1.66-2.32, respectively) and DFS (HR = 2.37, 95% CI: 1.19-4.72 and HR = 2.18, 95% CI: 1.61-2.96, respectively). In addition, over-expression of Smo was associated with poor DFS (HR = 1.38, 95% CI: 1.08-1.75). CONCLUSIONS: This study reveals that over-expressed Hh pathway components, including Shh, Gli1 and Smo, are associated with poor prognosis in digestive system cancer patients. Hh signaling pathway may become a potential therapeutic target in digestive system cancers. Show more

Keywords: Hedgehog signaling pathway, digestive system cancers, meta-analysis, prognosis

DOI: 10.3233/CBM-150542

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 71-79, 2016

Authors: Yang, Jingke | Xiao, Xiang | Li, Ruijuan | Li, Zijian | Deng, Mingyang | Zhang, Guangsen

Article Type: Research Article

Abstract: BACKGROUND: Aberrant DNA methylation status of some genes has been shown to be involved in chemoresistance of acute myeloid leukemia (AML). We have recently found that down-regulation of the β subunit of mitochondrial ATP synthase (ATPsyn-β) leads to adriamycin resistance in acute and chronic myeloid leukemia cells, and hypermethylation of the ATPsyn-β gene promoter is associated with chemoresistance in chronic myeloid leukemia. OBJECTIVE: To further investigate the relationship between methylation of ATPsyn-β gene, mRNA expression as well as chemoresistance in AML. METHODS: Quantitative RT-PCR and methylation specific PCR were performed …to assess mRNA expression and methylation status of ATPsyn-β gene on primary bone marrow nuclear cells (BMMCs), and cell proliferation assay was used to determine the sensitivity of BMMCs to adriamycin. RESULTS: Hypermethylation status of ATPsyn-β gene promoter existed in those relapsed/refractory AML patients, and this hypermethylation of the gene was associated with a suppressed mRNA expression levels. Four patients at diagnosis and relapse underwent gene methylation status shift from hypermethylation to hypomethylation, which was accompanied by reduced mRNA expression of the gene. 5-azacitidine(5-Aza)- a demethylating agent, could restore ATPsyn-β mRNA expression and increase the adriamycin sensitivity of primary leukemic cells from seven relapsed/ refractory AML patients. CONCLUSIONS: Hypermethylation of ATPsyn-β gene promoter is associated with a down-regulated mRNA expression and chemoresistance in AML patients. Show more

Keywords: Methylation, mitochondrial ATP synthase, chemoresistance, acute myeloid leukemia

DOI: 10.3233/CBM-150543

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 81-88, 2016

Authors: Lv, Yang | Ding, Xuan-Sheng | Li, Yan | An, Xiang | Miao, Li-Yun

Article Type: Research Article

Abstract: BACKGROUND: Chemotherapy-related hepatic dysfunction affected the prognosis of non-small cell lung cancer (NSCLC). However, predictive factors of chemotherapy-related hepatic dysfunction remained undefined. OBJECTIVE: To identify the predictive factors for hepatic dysfunction during cytotoxic chemotherapy in Chinese patients with advanced NSCLC. METHODS: We retrospectively reviewed the medical records of patients with advanced NSCLC who received cytotoxic chemotherapy at Division of Respiratory Medicine, the affiliated Drum Tower Hospital of Nanjing University, from July 2012 to January 2015. We investigated the incidence of hepatic dysfunction during chemotherapy and evaluated several clinical factors that are associated with …hepatic dysfunction, including body mass index (BMI) and high density lipoprotein cholesterol (HDL-C). RESULTS: A total of 116 patients were enrolled in study, 54 patients (46.57%) experienced hepatic dysfunction after receiving chemotherapy. Multivariate analysis for hepatic dysfunction in patients with advanced NSCLC showed that hepatic dysfunction was associated with higher BMI (odds ratio = 4.742, P = 0.001) and lower HDL-C (odds ratio = 3.018, P = 0.019). Pearson's rank correlation analysis revealed that HDL-C and BMI presented a negative correlation in patients with hepatic dysfunction (r = -0.487, P < 0.001). CONCLUSIONS: Higher BMI and lower HDL-C levels seem to be good independent predictive factors for chemotherapy-related hepatic dysfunction in advanced NSCLC. In addition, a negative correlation was presented between BMI and HDL-C. Show more

Keywords: NSCLC, chemotherapy, hepatic dysfunction, BMI, HDL-C

DOI: 10.3233/CBM-150544

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 89-97, 2016

Authors: Zavala, Valentina | Pérez-Moreno, Elisa | Tapia, Teresa | Camus, Mauricio | Carvallo, Pilar

Article Type: Research Article

Abstract: BACKGROUND: Mechanisms that lead to the reduced expression of BRCA1 in triple-negative breast cancer (TNBC) tumors are not fully understood. A possible cause is overexpression of miR-146a and miR-638, which regulate BRCA1 expression in other cancers. OBJECTIVE: To evaluate the expression of these microRNAs in relation to BRCA1 expression in TNBC tumors. METHODS: Expression of both microRNAs was assessed by real time qPCR using Taqman microRNA assays in TNBC tumors. Results were related to protein expression of BRCA1 and patient's survival. RESULTS: miR-146a and miR-638 were overexpressed in 36% and …59% of TNBC tumors, respectively. Overexpression was preeminent in BRCA1-deficient tumors and significantly associated to a better overall survival. CONCLUSION: Both miRNAs are potential biomarkers for improved overall survival in patients with BRCA1-deficient TNBC tumors. Show more

Keywords: BRCA1, breast cancer, microRNA, miR-146a, miR-638, triple negative breast cancer

DOI: 10.3233/CBM-150545

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 99-107, 2016

Authors: Eskandari-Nasab, Ebrahim | Hashemi, Mohammad | Ebrahimi, Mahboubeh | Amininia, Shadi

Article Type: Research Article

Abstract: Nuclear factor kappaB (NF-kB) plays a key role in mammary gland development and breast cancer (BC) progression. A functional -94 insertion/deletion ATTG polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to affect NF-KB1 expression and confer susceptibility to different types of cancer. The current study aimed to assess the association of NFKB1 -94 insertion/deletion ATTG promoter polymorphism and BC risk in an Iranian population. A total of 439 subjects including on 236 BC patients and 203 healthy women were recruited. The NF-KB1 -94ins/del ATTG polymorphism was genotyped by Allele-Specific polymerase chain reaction (AS-PCR) method. Our results demonstrated …that the NF-KB1 -94ins/del ATTG polymorphism was associated with a reduced risk of BC in Codominant (Ins/Ins vs. Del/Del: OR = 0.33, 95%CI = 0.17-0.64; P= 0.001), dominant (Ins/Ins vs. Ins/Del+Del/Del: OR = 0.64, 95%CI = 0.42-0.97; P= 0.027) and recessive (Ins/Del+Del/Del vs. Del/Del: OR = 0.40, 95%CI = 0.21-0.75; P= 0.002) tested inheritance models. Additionally, the Del allele of NF-KB1 -94ins/del ATTG variation with a higher prevalence in the control group compared to the BC patients (43.3% vs. 33.5%) was associated with a decreased risk of BC (OR = 0.66, 95%CI = 0.50-0.86, P= 0.003). In conclusion, our findings for the first time, suggest that the NF-KB1 -94ins/del Del allele and Del/Del genotype were associated with a reduced risk of BC which may contribute as protective factors against BC. Show more

Keywords: NF-kB, breast cancer, deletion polymorphism

DOI: 10.3233/CBM-150546

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 109-115, 2016

Authors: Bergis, Dominik | Kassis, Valentin | Radeke, Heinfried H.

Article Type: Research Article

Abstract: BACKGROUND: Gastric cancer (GC) is one of the most common and devastating tumor conditions. Its development is closely linked to an infection with Helicobacter pylori and chronic, cytokine-driven inflammation. The proinflammatory cytokine Interleukin-33 (IL-33), its membrane bound cellular receptor ST2L and its soluble receptor sST2 have recently been identified as important factors in various tumor conditions, but their role in GC remains ill-defined. METHODS: Thirty patients with adenocarcinoma of the stomach or the esophagogastric junction were prospectively enrolled in the current study. 51 patients with Helicobacter pylori positive or negative gastritis and 40 healthy volunteers served …as control group. Levels of IL-33 and sST2 were determined by ELISA and their relation to HP-status, tumor stage and survival was assessed. RESULTS: Soluble ST2 levels in GC were significantly higher than in gastritis or healthy controls (p< 0.0001). Furthermore, higher levels of sST2 were seen in patients with lower degree of tumor differentiation. Soluble ST2 was significantly associated with a more advanced tumor stage (p= 0.018), metastatic disease (p= 0.014) and significantly correlated with the duration of the disease (p= 0.0017). Calculating the ratio of IL-33/sST2 allowed the discrimination of tumor and non-tumor patients. CONCLUSION: Soluble ST2 is associated with advanced and metastatic disease in GC patients and significantly correlates with the duration of the disease. The IL-33/sST2 ratio may offer a new, interesting approach in identifying GC patients. Show more

Keywords: Gastric cancer, inflammation, interleukin-33, sST2, Helicobacter pylori

DOI: 10.3233/CBM-150547

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 117-125, 2016

Authors: He, Ying-Chun | Shen, Yi | Cao, Yu | Tang, Fang-Qing | Tian, Dao-Fa | Huang, Chen-Fei | Tao, Huai | Zhou, Fang-Liang | Zhang, Bo | Song, Lan | He, Lan | Lin, Li-Mei | Lu, Fang-Guo | Liao, Duan-Fang | Cao, Deliang

Article Type: Research Article

Abstract: BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Southern China. Aldo-keto reductase 1B10 (AKR1B10) is upregulated in multiple tumors and plays an oncogenic role. OBJECTIVE: To examine the expression of AKR1B10 at mRNA and protein levels in nasopharyngeal tumors and correlate its expression with clinicopathological parameters. METHODS: A tissue microarray, paraffin blocks, and frozen surgical nasopharyngeal samples were procured. Western blot and immunohistochemistry were used to estimate AKR1B10 protein expression, and mRNA levels were detected by real time RT-PCR. RESULTS: We found that AKR1B10 expression was …increased in malignant tissues compared to the normal tissues (p= 0.000). In NPC tissues, AKR1B10 expression appeared high specifically in squamous cell carcinoma, but low in basal cell carcinoma, adenoid cystic carcinoma, adenocarcinoma and undifferentiated carcinoma (p= 0.000). AKR1B10 expression also demonstrated correlation with tumor differentiation, with a high level in well and moderately differentiated but a low level in poorly differentiated carcinoma (p= 0.000). AKR1B10 was also upregulated in hyperplasia and benign tumors (p= 0.000), and demonstrated a specific nuclear distribution in these non-cancerous diseases. CONCLUSIONS: AKR1B10 is overexpressed in nasopharyngeal hyperplasia, benign tumors, and carcinomas, being a potential new biomarker. Show more

Keywords: Aldo-keto reductase 1B10, AKR1B10, nasopharyngeal carcinoma, hyperplasia, biomarker

DOI: 10.3233/CBM-150548

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 127-135, 2016

Authors: Li, Ke-Yi | Zhang, Jie | Jiang, Li-Cheng | Zhang, Bin | Xia, Chun-Peng | Xu, Kai | Chen, Hai-Ying | Yang, Qiao-Zhi | Liu, Shu-Wei | Zhu, Hong

Article Type: Research Article

Abstract: This article has been retracted, and the online PDF has been watermarked ``RETRACTION''. The retraction notice is available at http://doi.org/10.3233/CBM219904.

Keywords: Drug target, oral squamous cell carcinoma, RNA interference, ubiquitin-specific proteases 39

DOI: 10.3233/CBM-150549

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 137-144, 2016

Authors: Nomura, Hiroyuki | Kataoka, Fumio | Aoki, Daisuke | Jinno, Hiromitsu | Kitagawa, Yuko | Sato, Yuji | Womack, Chris | Wombwell, Helen | Hodgson, Darren | O'Connor, Mark | Harbron, Chris | Yin, Xiaolu

Article Type: Research Article

Abstract: BACKGROUND: Poly(ADP)-ribose polymerase (PARP) inhibitors such as olaparib can induce cell death in cancer cells with homologous recombination (HR) DNA repair deficiencies, such as BRCA1/2 mutations. AIM: To identify prognostic biomarkers of long-term outcomes in cancer patients. METHODS: Immunohistochemistry was used to analyse expression of key HR pathway proteins (ATM, ATR, BRCA1, MDC1, MRE11) and PARP-1 in 100 serous ovarian cancer (SOC) and 100 triple-negative breast cancer (TNBC) tumour samples from Japanese patients. RECIST assessment was used. RESULTS: Patient demographic data and BRCA1/2 mutation status were unavailable. Most …proteins listed previously were detected in > 80% of tissue samples, with BRCA1 expression detected in 60-65%. A potential link between BRCA1 expression and overall survival (M stage adjusted) in SOC patients was observed, but was not statistically significant after multiple testing adjustment. Correlations between other biomarker expression and survival were not observed. In TNBC patients, MDC1 staining was associated with progressive disease, but this was not statistically significant; the analysis did not identify significant correlations between biomarker expression and disease control. Limited event numbers prevented assessment of the prognostic value of BRCA1 in TNBC. CONCLUSION: BRCA1 expression may be a candidate for a prognostic biomarker in SOC. Further studies are warranted. Show more

Keywords: BRCA, ovarian cancer, breast cancer, biomarker

DOI: 10.3233/CBM-150550

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 145-152, 2016

Authors: Lyubchenko, Ludmila | Emelyanova, Marina | Shamanin, Vladimir | Demidov, Lev | Zasedatelev, Alexander | Nasedkina, Tatyana

Article Type: Research Article

Abstract: BACKGROUND: The activating mutation BRAF V600E is considered to be a diagnostic cutaneous melanoma (CM) marker important for prognosis and targeted therapy. OBJECTIVE: The aim of this study was to determine the frequency of the V600E mutation in CM patients in Russia and to estimate the influence of the BRAF gene mutation status on prognosis and clinical outcome. METHODS: To ensure mutation detection in FFPE tissue, interlaboratory validation was performed using three different methods: allele-specific hybridisation on a biochip, allele-specific real-time PCR and, in some cases, direct sequencing. RESULTS: …Mutation V600E was detected in 49% of patients. The age of disease manifestation was significantly lower in mutated (MT) BRAF patients, and the median age difference between the wild-type (WT) and MT BRAF groups (P= 0.002) was 10 years. A tumour thickness more than 1 mm was also more frequently observed in the MT BRAF group (P= 0.059). Patients from the MT BRAF group were more likely to have ulceration compared to the WT group (P= 0.088). No statistically significant differences were found between the relapse-free, progression-free or overall survival of CM patients in the MT BRAF and WT BRAF groups. CONCLUSIONS: The data obtained show that the V600E BRAF mutation occurred in about half of melanoma patients; it was associated with earlier manifestation of melanoma and likely with more aggressive clinical features. Show more

Keywords: Cutaneous melanoma, BRAF gene, V600E mutation, molecular diagnostics, clinical features

DOI: 10.3233/CBM-150551

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 153-160, 2016

Authors: Qin, Meilin | Liu, Gang | Huo, Xisong | Tao, Xuemei | Sun, Xiaomeng | Ge, Zhouhong | Yang, Juan | Fan, Jia | Liu, Lei | Qin, Wenxin

Article Type: Research Article

Abstract: BACKGROUND: It has been shown that circular RNA (circRNA) is associated with human cancers, however, few studies have been reported in hepatocellular carcinoma (HCC). OBJECTIVE: To estimate clinical values of a circular RNA, Hsa_circ_0001649, in HCC. METHODS: Expression level of hsa_circ_0001649 was detected in HCC and paired adjacent liver tissues by real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs). Differences in expression level of hsa_circ_0001649 were analyzed using the paired t-test. Tests were performed between clinical information and hsa_circ_0001649 expression level by analysis of variance (ANOVA) or welch t-test and a receiver operating characteristics …(ROC) curve was established to estimate the value of hsa_circ_0001649 expression as a biomarker in HCC. RESULTS: hsa_circ_0001649 expression was significantly downregulated in HCC tissues (p = 0.0014) based on an analysis of 89 paired samples of HCC and adjacent liver tissues and the area under the ROC curve (AUC) was 0.63. Furthermore, hsa_circ_0001649 expression was correlated with tumor size (p = 0.045) and the occurrence of tumor embolus (p = 0.017) in HCC. CONCLUSIONS: We first found hsa_circ_0001649 was significantly downregulated in HCC. Our findings indicate hsa_circ_0001649 might serve as a novel potential biomarker for HCC and may function in tumorigenesis and metastasis of HCC. Show more

Keywords: Circular RNA, hsa_circ_0001649, hsa_circ_001599, hepatocellular carcinoma, biomarker

DOI: 10.3233/CBM-150552

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 161-169, 2016

Authors: Saito, Masaya | Yano, Yoshihiko | Hirano, Hirotaka | Momose, Kenji | Mouri, Kentaro | Hishimoto, Akitoyo | Yoshida, Masaru | Azuma, Takeshi

Article Type: Research Article

Abstract: BACKGROUND AND AIM: Alcoholic liver disease (ALD) is the most common cause of hepatocellular carcinoma (HCC) worldwide. Des-gamma-carboxy prothrombin (DCP) is elevated in many patients with HCC, but also in severe alcoholics without HCC. We aimed to clarify whether the DCP/NX-DCP ratio (NX-DCP-R) could have a high specificity in ALD patients without HCC. METHODS: We performed a prospective cohort study on a total of 703 consecutive outpatients of liver diseases including severe alcoholics and healthy volunteers, who underwent blood biochemical examinations at Kobe University Hospital. Serum DCP was measured by electrochemiluminescence immunoassay (ECLIA) using a monoclonal …antibody, MU-3. A novel parameter, serum NX-DCP, which represents predominantly DCP caused by reduced vitamin K availability, was also measured by ECLIA using monoclonal antibodies P-16 and P-11. The diagnostic accuracy of DCP and NX-DCP-R in patients with and without excessive alcohol intake was statistically examined. RESULTS: DCP was significantly higher in alcoholics than in non-alcoholics (p= 0.005), whereas the NX-DCP-R did not differ between alcoholics and non-alcoholics (p= 0.375). DCP was significantly increased in the serum of each patient with alcoholic hepatitis and alcoholic cirrhosis (p< 0.05), whereas the NX-DCP-R was not increased (p> 0.05). CONCLUSIONS: NX-DCP-R, but not DCP, was not increased in alcoholics without HCC. As for negative screening for HCC, the specificity of the NX-DCP-R in alcoholics without HCC was better than that of DCP in alcoholics without HCC, and so could be a useful negative screening tool for HCC in millions of alcoholics worldwide. Show more

Keywords: NX-PVKA, vitamin K deficiency, warfarin, Tumor Node Metastasis, Child's grade

DOI: 10.3233/CBM-150553

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 171-180, 2016

Authors: Makhlouf, Manal Mohamed

Article Type: Research Article

Abstract: BACKGROUND: Abnormalities in the control of apoptosis play an important role in leukemogenesis. Survivin is a member of inhibitor of apoptosis proteins family, it prevents apoptosis by blocking caspase activity and play a role in cell proliferation. While, cyclin E2 is one of the cyclins proteins family that controls progression of cell cycle by activation of cyclin dependant-kinase. OBJECTIVE: Was to assess survivin and cyclin E2 genes expression in acute leukemia (AL) patients, and to define their role in the susceptibility of AL, and their correlation with the clinical presentation, laboratory findings, as well as treatment …outcome. PATIENTS AND METHODS: This study included 60 de novo AL patients and 40 control subjects to study the expression of survivin and cyclin E2 genes using RT-PCR. RESULTS: Survivin and cyclin E2 genes expression was significantly higher in leukemic patients compared with control subjects (P< 0.001), both genes separately were associated with increased risk of leukemia development and treatment failure (P< 0.01). Moreover, when combining the 2 genes expression, a significant elevation of the risk of leukemia and treatment failure was found (P < 0.01). CONCLUSIONS: Survivin and cyclin E2 genes expression may have clinical relevance and can be considered as molecular risk factors for AL. Also they may be useful as predictive markers for treatment outcome in leukemic patients. Show more

Keywords: Survivin, cyclin E2, acute leukemia, RT-PCR

DOI: 10.3233/CBM-150554

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 181-189, 2016

Authors: Reyes, Niradiz | Benedetti, Ines | Bettin, Alfonso | Rebollo, Juan | Geliebter, Jan

Article Type: Research Article

Abstract: BACKGROUND: Fibromodulin is a small leucine-rich proteoglycan important for extracellular matrix organization and essential for tissue repair in multiple organs. The main function of this proteoglycan is the regulation of collagen fibrillogenesis; however, more recently described roles for fibromodulin have expanded to include regulation of angiogenesis, reprogramming of human fibroblasts into pluripotent cells, modulation of TGF-β activity, inflammatory processes and association with metastatic phenotypes. Additionally, fibromodulin has been identified as a novel tumor-associated antigen in leukemia, lymphoma, and leiomyoma. Knowledge about its expression in the prostate is limited. METHODS: Fibromodulin expression was analyzed in two …different malignant and one non-tumorigenic prostatic cell lines in culture, and in benign and malignant human prostate tissue. Expression was analyzed by real time PCR, immunocytochemistry, and immunohistochemistry. DNA sequencing was performed on a PCR fragment amplified with primers specific for the FMOD gene from cDNA obtained from the cultured cell lines. RESULTS: Both immunostaining and real time PCR analysis of cell lines indicated that fibromodulin was differentially expressed in the cancerous cell lines compared to the non-tumorigenic cell line. Likewise, cancerous tissue expressed significantly higher levels of intracellular fibromodulin compared to matched, benign tissue from the same patients, as well as compared to tissue from patients with only benign disease. CONCLUSIONS: The expression of fibromodulin was higher in prostatic cancer cells (cell-lines and human tissue) than in normal/benign prostatic cells. Additional studies are required to determine the biological and clinical significance and whether this proteoglycan has a role in carcinogenesis of the prostate or in prostate cancer related inflammatory processes. Show more

Keywords: Fibromodulin, extracellular matrix, inflammation, immunohistochemistry, corpora amylacea, prostate cancer

DOI: 10.3233/CBM-150555

Citation: Cancer Biomarkers, vol. 16, no. 1, pp. 191-202, 2016