Cancer Biomarkers - Volume 13, issue 6

Authors: Bobrowska-Korczak, Barbara | Skrajnowska, Dorota | Tokarz, Andrzej

Article Type: Research Article

Abstract: Backround: Epigenetic alterations have been identified as promising new targets for cancer prevention strategies as they occur early during carcinogenesis and represent potentially initiating events for cancer development. Objective: The aim of the present study was to assess the effect of zinc and copper on the DNA methylation in rats whose breast adenocarcinoma was simultaneously induced with 7, 12 dimethylbenz[a]anthracene (DMBA). The reseach focused on the kinetics of alterations in urinary 5-MedC (5-methyl-2’-deoxycytidine) at the early and late stages of carcinogenesis, as well as the influence of dietary factors on the process. Methods: The content of …5-methyl-2’-deoxycytidine in the rats’ urine was determined by the ELISA (enzyme-linked immunosorbent assay) method. The 5-MedC level was standardized by conversion to the creatinine level. Results: It was found that in the rats fed only the standard diet and DMBA-treated the urinary levels of 5-MedC collected after the 10th week were considerably lower in comparison with the content of this biomarker in urine starting from the 19th week (43.56 ± 14.34 vs. 71.84 ± 42.64). The animals treated with DMBA and additionally obtaining copper were characterized by a much higher content of the examined biomarker in urine, both in the early phase of carcinogenesis (10th week) and later (19th week), as compared with the animals fed only the standard diet or the zinc-supplemented diet. In the rats with a fully developed tumor (100% incidence of the disease) the applied dose of resveratrol (0.2 mg/kg bw) was too low to prevent the intensive formation and increase of 5-MedC level in urine, additionally stimulated by the presence of Cu in the diet as well as by the active, ongoing neoplastic process. Conclusions: Summing up the obtained results of investigations it can be said that the urinary level of 5-MedC depends on the applied supplementation. Show more

Keywords: Biomarkers, methylation, copper, zinc, resveratrol

DOI: 10.3233/CBM-130384

Citation: Cancer Biomarkers, vol. 13, no. 6, pp. 403-410, 2013

Authors: Xu, Ting | Zou, Qing | Wu, Jing | Yu, Bin | Xu, Zicheng | Cai, Hongzhou | Zhang, Wei

Article Type: Research Article

Abstract: Objective: To examine the expression of heterogeneous nuclear ribonucleoprotein U-like 1 (hnRPUL1) and poly (ADP-ribose) polymerase 1 (PARP-1) in renal cell carcinoma (RCC) tissues and the connection between the expressions and prognosis of RCC. Material and Methods: Total RNAs were extracted from 36 pairs of RCC and their adjacent non-tumor tissues and real-time qRT-PCR was performed. Results: The expression of hnRPUL1 was remarkably downregulation in RCC tissues (14/36, 38.9%), compared with matched adjacent non-tumor tissues. And the expression of PARP1 was also remarkably downregulation in RCC tissues (12/36, 30.0%). In the stratification of clinical stage, downregulation …in hnRPUL1 and PARP1 were both connected with the advanced clinical stage (P=0.013 and P=0.009). In addition, significantly increased risk of developing with a moderately and poorly differentiated tumor nuclear grade was found in the downregulation of hnRPUL1 patients (P=0.027). Conclusions: Despite the limitations, hnRPUL1 and PARP1 were downregulated in renal cell carcinoma and connected with the prognosis. Show more

Keywords: Heterogeneous nuclear ribonucleoprotein U-like 1, Poly (ADP-ribose) polymerase 1, renal cell carcinoma

DOI: 10.3233/CBM-140390

Citation: Cancer Biomarkers, vol. 13, no. 6, pp. 411-415, 2013

Authors: Malekzadeh, Mahyar | Dehaghani, Alamtaj Samsami | Ghaderi, Abbas | Doroudchi, Mehrnoosh

Article Type: Research Article

Abstract: Background: IL-17A a member of IL-17 family of cytokines is an inflammatory cytokine produced by a subset of CD4+ T cells that links innate and adaptive immunity. IL-17A has been shown to be a key mediator of inflammation in autoimmune diseases, transplant rejection and cancers. Objective: To investigate the level of IL-17A in sera of southern Iranian patients with papillary serous cystadenocarcinoma of ovary and compare it with age-matched women of the same region. Methods: In this study we investigated IL-17A and CA125 levels in sera of 26 patients with ovarian serous cystadenocarcinoma and 62 healthy …age matched women by commercial ELISA assays. Results: Fifteen (58%) and 16 (61.5%) out of 26 patients showed elevated IL-17A (1.25 ± 2.25 pg/ml) and CA125 (218 ± 224.69 IU/ml) in their sera, respectively. No healthy individual had detectable IL-17A or elevated CA125 in their sera (8.85 ± 2.86 IU/ml). The mean IL-17A levels in poorly differentiated tumors (3.33 ± 2.36 pg/ml) was significantly higher than that of well differentiated (0.14 ± 0.38 pg/ml) and moderately differentiated (undetectable) tumors. There was also a positive correlation between IL-17A and CA125 in sera of patients and controls when grouped together (r=0.37, p=0.005). Conclusion: Elevation of IL-17A in a high percentage of ovarian serous cystadenocarcinoma and lack of this cytokine in healthy individuals makes it a specific candidate in diagnosis, follow up or immunotherapy. Show more

Keywords: Serous cystadenocarcinoma, ovarian tumor, IL-17A, CA125

DOI: 10.3233/CBM-140392

Citation: Cancer Biomarkers, vol. 13, no. 6, pp. 417-425, 2013

Authors: Milanizadeh, Saman | Khanyaghma, Mahsa | Haghighi, Mahdi Montazer | Mohebbi, Seyedreza | Damavand, Behzad | Almasi, Shohreh | Azimzadeh, Pedram | Zali, Mohammadreza

Article Type: Research Article

Abstract: Background: Single nucleotide polymorphisms in mismatch repair genes may be associated with different protein expression, production, and efficiency according to allele status and influence the risk of developing colorectal cancer. Objective: This research aimed at analyzing two important polymorphisms in MLH1 gene and their association in colorectal cancer susceptibility. Methods: In total, 219 CRC patients and 248 healthy controls were genotyped with PCR/RFLP for I219V and IVS12-169 C>T polymorphisms in MLH1 gene. Sequencing performed to ensure work flow and results. We used unconditional logistic regression after adjusting for age and sex to evaluate the association between …each polymorphism and colorectal cancer. Results: The MLH1 I219V polymorphism was associated with colorectal cancer susceptibility (P=0.01). Stratified data analysis for gender demonstrated association of AG (P=0.009) and GG (P=0.021) genotypes with risk of colorectal cancer in women. In contrast there is no association with IVS 12-169 C>T polymorphism and colorectal cancer risk. Conclusions: I219V SNP might be a susceptibility factor for CRC and gender is a factor that must be considered when it is analyzing. Further tests need to be done to define it as a dependable prognosis factor. Show more

Keywords: Colorectal cancer, MLH1, PCR, RFLP

DOI: 10.3233/CBM-140391

Citation: Cancer Biomarkers, vol. 13, no. 6, pp. 427-432, 2013

Authors: Nie, Xin | Cheng, Gang | Ai, Bin | Zhang, Shuai

Article Type: Research Article

Abstract: Background: Ribonucleotide reductase subunit M1 (RRM1) has emerged as a promising biomarker to predict the efficacy of gemcitabine. The purpose of the study was to evaluate whether the tailored chemotherapy based on RRM1 immunohistochemical (IHC) expression had any benefit for patients with advanced non-small cell lung cancer (NSCLC). Methods: A single-institution study was conducted in patients with advanced NSCLC. In personalized therapy group, patients received chemotherapy based on RRM-1 IHC expression levels. Low RRM1 group received gemcitabine or gemcitabine/cisplatin, high RRM1 group received docetaxel or docetaxel/ cisplatin. In standard therapy group, non-customized chemotherapy was delivered. In this trial, …Patients aged ≥ 70 years received single agent chemotherapy, whereas patients below 70 had platinum-based chemotherapy. Results: There were statistically significant improvements between the personalized therapy group versus the standard therapy group in disease control rate (82.9% vs 55.3%, P=0.004), and PFS (median: 5.5 months vs 3.0 months, P=0.005). Besides, the OS had a tendency to become more prolonged (median: 16.0 months vs 12.4 months, P=0.286). The subgroup analysis suggested the survival benefit in the elderly patients was more obvious. Conclusion: RRM1 IHC expression tailored selection of first-line therapy could improve therapeutic outcomes in patients with advanced NSCLC. Show more

Keywords: RRM1, immunohistochemistry, advanced non-small cell lung cancer, tailored chemotherapy

DOI: 10.3233/CBM-130381

Citation: Cancer Biomarkers, vol. 13, no. 6, pp. 433-440, 2013

Authors: Çekiç, Erdinç | Sürmelioǧlu, Özgür | Tarkan, Özgür | Özdemir, Süleyman | Uǧuz, Aysun | Kıroǧlu, Mete

Article Type: Research Article

Abstract: Background: The general prognostic factors in larynx tumors are believed to be tumor stage, anatomical location, histological differentiation and the presence of neck metastasis. Effects of tumor invasion to sub-regions of larynx (anterior commissure, ventricle, subglottic space) and over-expression of p53, c-erb-B2 and Ki67 detected immunohistochemically on development of recurrence in patients were investigated in this study. Methods: Twenty patients (Group 1) in whom recurrence had developed and 20 others (Group 2) without recurrence during follow-up were included in this study. Results: Both the anterior commissure and ventricle involvements were found to be more frequent in …patients with recurrence. But statistically significant difference was detected with only ventricular involvement (p=0.025). After Immunohistochemical evaluation none of the 3 immunohistochemical parameters were found to be higher in the recurrence group and not any of them showed a statistically significant difference between two groups. Conclusion: Only ventricle involvement may be a predictor factor for recurrence. Show more

Keywords: Larynx cancer, recurrence, p53, Ki67, c-erb-B2

DOI: 10.3233/CBM-130380

Citation: Cancer Biomarkers, vol. 13, no. 6, pp. 441-446, 2013

Authors: Ma, Ruo-Lan | Min, Li | Chen, Duo | Tao, Wei-Ping | Ge, Wei | Wu, Yao-Gui

Article Type: Research Article

Abstract: N-acetyltransferase 2 (NAT2) gene encodes a phase II enzyme taking part in detoxification of aromatic amines. Published studies have demonstrated that N-Acetyltransferase 2 (NAT2) phenotype is a risk factor of various cancers. Many studies have investigated the association between NAT2 phenotype and susceptibility to esophageal cancer but yielded controversial results. To derive a more precise estimation of this association, a meta-analysis was performed. Electronic databases (Pubmed/Medline, ISI Web of Science and China National Knowledge Infrastructure) in English and Chinese were searched. A total of 5 articles including 476 cases and 1,093 controls were included in this meta-analysis. Odds ratio (OR) …with 95% confidence interval (95% CI) was used to evaluate intensity of associations. Pooling studies together, NAT2 slow acetylator phenotype was a significant risk factor of esophageal squamous cell cancer (OR=1.35, 95% CI=1.03–1.77, n=5 studies) but not esophageal adenocarcinoma (OR=0.97, 95% CI=0.47–2.04, n=2 studies). There was a significant association between NAT2 acetylator phenotypes and ESCC in South Asian populations (OR=1.51, 95% CI=1.03–2.20), but not in East Asian populations (OR=1.19, 95% CI=0.80–1.77). Significant association between NAT2 acetylator phenotypes and esophageal cancer was found in population-based control subgroup (OR=1.63, 95% CI=1.07–2.50) but not in hospital-based control subgroup (OR=1.19, 95% CI=0.84–1.69). There is a significant association between NAT2 acetylator phenotype and esophageal cancer in both smokers (OR=1.681, 95% CI=1.179–2.395) and non-smokers (OR=1.614, 95% CI=1.173–2.222). In conclusion, NAT2 slow acetylator phenotype was a significant risk factor of ESCC in Asian populations. Show more

Keywords: N-acetyltransferase 2, esophageal cancer, risk, meta analysis

DOI: 10.3233/CBM-130387

Citation: Cancer Biomarkers, vol. 13, no. 6, pp. 447-455, 2013

Authors: Du, Wei | Ma, Xuelei | Kong, Weiqi | Liu, Tao | Wei, Benling | Yu, Jiayun | Li, Yanyan | Huang, Jingwen | Li, Zikang | Liu, Lei

Article Type: Research Article

Abstract: Background: MicroRNAs (miRNAs) are small non-coding RNAs of 20–22 nucleotides in length, which regulate the translation or degradation of human messenger RNA (mRNA). MiRNAs involve in the regulation of most biological processes, as well as human diverse diseases including cancer. Recently, many studies investigated the association between miR-196a2 rs11614913 polymorphism and colorectal cancer (CRC), which showed inconclusive results. Methodology/Principal Findings: We conducted a meta-analysis of 6 studies that included 1800 cases and 2329 controls. There was a statistically decreased risk of CRC in dominant model, recessive model and homozygous model. In the Asian group, significantly decreased susceptibility of …CRC was found in allele model, dominant model, recessive model and homozygous model. As for the Caucasian group, none of genetic models demonstrates significant association between miR-196a2 rs11614913 polymorphism and susceptibility of CRC. Conclusions: These findings supported that miR-196a2 rs11614913 polymorphism may contribute to the susceptibility of CRC. Show more

Keywords: Colorectal cancer, miR-196a2, polymorphism

DOI: 10.3233/CBM-140389

Citation: Cancer Biomarkers, vol. 13, no. 6, pp. 457-464, 2013

Authors: Gao, Xueren | Duan, Haixia | Zhu, Zhansheng

Article Type: Research Article

Abstract: Background: PTEN, a candidate tumor suppressor gene, has been identified within chromosome 10q23 and plays an important role in tumorigenesis. The association between the IVS4 insertion/deletion (I/D) polymorphism of PTEN and cancer risk in several populations has been studied, but results are conflicting. The aim of the present study was to investigate association of PTEN IVS4 polymorphism with cancer risk by conducting a meta-analysis. Methods: A literature search was conducted through PubMed, Chinese National Knowledge Infrastructure (CNKI) and WanFang databases (up to October 18, 2013). Six eligible studies with 2,179 cases and 3,132 controls were enrolled in the …meta-analysis. The pooled odds ratio (OR) and 95% confidence intervals (CI) were used to assess the strength of association. Results: Our results indicated that the polymorphism conferred a significantly decreased risk of overall cancer (dominant model: OR=0.87, 95% CI 0.77–0.99; recessive model: OR=0.83, 95% CI: 0.72–0.96; II vs. DD model: OR=0.79, 95% CI: 0.67–0.94; I vs. D model: OR=0.89, 95% CI: 0.82–0.97). Subgroup analysis by cancer type and ethnicity furtherly showed that PTEN gene IVS4 polymorphism was associated with decreased risk of digestive cancers (recessive model: OR=0.77, 95% CI: 0.64–0.92; II vs. DD model: OR=0.72, 95% CI: 0.58–0.91; I vs. D model: OR=0.84, 95% CI: 0.76–0.94), this strong association with reduced risk of cancer was also found in Asian population (recessive model: OR=0.83, 95% CI: 0.71–0.98; II vs. DD model: OR=0.79, 95% CI: 0.65–0.96; I vs. D model: OR=0.89, 95% CI: 0.81–0.98). Conclusion: In conclusion, our meta-analysis suggested that PTEN IVS4 polymorphism might play a protective role in the development of cancer, further independent confirmation of associations observed in PTEN IVS4 polymorphism by more studies was necessary. Show more

Keywords: PTEN, polymorphism, cancer risk, meta-analysis

DOI: 10.3233/CBM-130386

Citation: Cancer Biomarkers, vol. 13, no. 6, pp. 465-470, 2013

Authors: Li, Yanyan | Ma, Xuelei | Zhao, Jingyi | Zhang, Binglan | Jing, Zhang | Liu, Lei

Article Type: Research Article

Abstract: Background: microRNA-210 expression in breast carcinoma represents an appealing prognostic tool, but no consensus exists on this debating topic. Objective: We conducted this comprehensive meta-analysis to summarize evidence for use of microRNA-210 to predict patients’ clinical outcomes. Methods: Relevant literatures were identified using Pubmed and EMBASE. Patients’ clinical characteristics and survival related data were extracted. Statistics extracted from Kaplan–Meier survival curves were calculated with methods developed by Parmar, Williamson, and Tierney, multivariate Cox hazard regression analysis data were used directly in Revman 5.0. Pooled hazard ratios (HRs) were calculated to evaluate the prognostic role of microRNA-210. …Results: Finally, 7 studies containing 822 patients were considered eligible, pooled HR (95% CI) of studies for overall survival was 3.94 (1.90–8.15), for disease/recurrence free survival was 3.47 (2.63–4.60) and for metastasis free survival was 2.70 (1.46–5.00). We then respectively grouped the meta-analysis by patients’ region (Asia and non-Asia), tumor estrogen receptor/ progesterone receptor/Her-2 expression status (positive or negative) and treatment strategy (preoperative systemic treatment or only surgery). All the subgroup analysis showed stable prognostic value. Conclusions: Over-expressed microRNA-210 demonstrated a significantly higher risk of recurrence, metastasis and overall decreased survival rates for breast cancer patients. Show more

Keywords: microRNA-210, breast cancer, prognostic factor, meta-analysis

DOI: 10.3233/CBM-130385

Citation: Cancer Biomarkers, vol. 13, no. 6, pp. 471-481, 2013