This meta-analysis was performed to assess whether epidermal growth factor receptor (EGFR) mutation status was associated with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy.

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may influence the risk of cancer, but the results are still debatable. Therefore, we performed a systematic review to provide a more complete picture and conducted a meta-analysis to derive a precise estimation. We searched PubMed, EMBASE, EBSCO, Google Scholar and China National Knowledge Infrastructure (CNKI) databases until April 2014 to identify eligible studies. Thirty-one studies with cancer patients and controls were included in the meta-analysis. Overall, the polled analysis revealed that the T-786C polymorphism was significantly associated with increased cancer risk under multiple genetic models (C vs T: OR=1.135, 95%CI=1.048-1.228; CC vs TT: OR=1.278, 95%CI=1.045- 1.562; TC vs TT: OR=1.136, 95%CI=1.023-1.261; CC+TC vs TT: OR=1.159, 95%CI=1.047-1.281; CC vs TC+TT: OR=1.204, 95%CI= 1.003-1.447). G894T was associated with significant risk for females (TT vs GG: OR=1.414, 95%CI=1.056-1.892; TT vs GT+GG: OR=1.356, 95%CI=1.108-1.661) and for breast cancer (T vs G: OR=1.097, 95%CI=1.001-1.203; TT vs GG: OR=1.346, 95%CI=1.012-1.789; TT vs GT+GG: OR=1.269, 95%CI=1.028-1.566). Increased susceptibility was revealed for prostate cancer with 4a/b (ba vs bb: OR=1.338, 95%CI=1.013-1.768; aa+ba vs bb: OR=1.474, 95%CI=1.002-2.170). This meta-analysis indicated that the eNOS T-786C polymorphism is associated with elevated cancer risk; the G894T polymorphism contributes to susceptibility to breast cancer and cancer generally in females; and the 4a/b polymorphism may be associated with prostate cancer risk.

Published studies have evaluated associations between the MDM2 SNP309T>G polymorphism and bladder cancer susceptibility. However, these generated inconsistent results. The aim of the present investigation was to quantify the strength of association between MDM2 SNP309T>G polymorphism and bladder cancer risk by conducting a meta-analysis. We searched PubMed and Embase for related studies that had been published in English before April 1, 2014 and associations were assessed by summarizing the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). Five case-control studies with a total of 972 cases and 1,012 controls were finally identified to be eligible for the meta-analysis. Overall, the results indicated that there was no significant association between the MDM2 SNP309T>G polymorphism and bladder cancer risk (for the allele model G vs. T: OR=1.08, 95% CI 0.85-1.36, p=0.54; for the co-dominant model GG vs. TT: OR=1.20, 95% CI 0.74-1.93, p=0.46; for the dominant model GG+GT vs. TT: OR=0.98, 95% CI 0.80-1.20, p=0.83; for the recessive model GG vs. GT+TT: OR=1.20, 95% CI 0.83-1.74, p=0.33). However, on subgroup analysis by ethnicity, significant associations were found in Caucasians in three models (for the allele model G vs. T: OR=1.41, 95% CI 1.10-1.81, p=0.006; for the co-dominant model GG vs. TT: OR=2.16, 95% CI 1.28-3.63, p=0.004; for the recessive model GG vs. GT+TT: OR=2.06, 95% CI 1.31-3.22, p=0.002). In summary, the present meta-analysis provides evidence that the genotype for the MDM2 SNP309T>G polymorphism may be associated with genetic susceptibility to bladder cancer among Caucasians.

A number of studies have reported relationships of CYP2E1 RsaI/PstI polymorphisms with susceptibility to lung cancer in Chinese population. However, the epidemiologic results have been conflictive rather than conclusive. The purpose of this study was to address the associations of CYP2E1 RsaI/PstI polymorphisms with lung cancer risk in Chinese population comprehensively.

The current large-scale meta-analysis was performed to reach a reliable conclusion on the association between X-ray repair cross-complementing 1 (xrcc1) rs1799782 and the development of lung cancer. Studies that investigated the association between rs1799782 and lung cancer risk were identified by searching PubMed. We calculated odds ratio (OR) with corresponding 95 % confidence interval (CI) for Trp/Trp vs Arg/Arg, Trp/Trp + Arg/Trp vs Arg/Arg, and Trp/Trp vs Arg/Trp + Arg/Arg contrast models. Combining all 25 studies, we yielded three summary ORs: 1.07 (95 % CI 0.92-1.23) for Trp/Trp vs Arg/Arg, 0.93 (95 % CI 0.87-1.00) for Trp/Trp + Arg/Trp vs Arg/Arg, and 1.08 (95 % CI 0.94-1.25) for Trp/Trp vs Arg/Trp + Arg/Arg, suggesting rs1799782 was not associated with overall risk of lung cancer. Strikingly, a significantly deceased risk was found among Caucasian populations (Trp/Trp + Arg/Trp vs Arg/Arg, OR = 0.86, 95 % CI 0.76-0.97). This study confirms that xrcc1 rs1799782 may lower the risk of lung cancer among Caucasians.

The +331G/A progesterone receptor (PgR) gene polymorphism may influence risk of endometrial cancer. However, data from published studies have been controversial. To evaluate whether combined evidence shows an association between this polymorphism and endometrial cancer, we considered all available studies in a meta-analysis.

Emerging evidence indicates that RUNX3 is a candidate tumor suppressor in several types of human tumors including hepatocellular carcinoma (HCC). However, the correlation between RUNX3 hypermethylation and incidence of HCC remains unclear. Here, we conducted a systematic review and meta-analysis aiming to comprehensively assess the potential role of RUNX3 hypermethylation in the pathogenesis of HCC. A detailed literature search was made from PubMed, EMBASE, and ISI web of knowledge to identify studies for related research publications. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data was performed. Odds ratio (OR) was calculated and summarized, respectively. Final analysis of 821 HCC patients from 14 eligible studies was performed. We observed that RUNX3 hypermethylation was significantly higher in HCC than in normal liver tissue, the pooled OR from eight studies including 382 HCC and 161 normal liver tissue (OR = 39.32, 95 % confidence interval (CI) = 13.72-112.7, p < 0.00001). The pooled analysis showed significantly increased OR of RUNX3 hypermethylation (OR = 5.4, 95 % CI = 2.06-14.17, p < 0.00001) in HCC tissues and non-tumor liver tissues. In addition, statistically significant OR of RUNX3 hypermethylation was obtained from non-tumorous liver tissue of HCC patients and normal liver tissue (OR = 12.57, 95 % CI = 3.56-44.35, p < 0.0001). The results of this meta-analysis suggest that RUNX3 hypermethylation may be implicated in the pathogenesis of HCC. Thus, detection of RUNX3 hypermethylation may be a helpful and valuable biomarker for diagnosis of HCC.

The genetic polymorphisms of glutathione S-transferase (GSTs) have been suspected to be related to the development of lung cancer while the current results are conflicting, especially in the Chinese population.

Understanding the heterogeneous drug response of cancer patients is essential to precision oncology. Pioneering genomic analyses of individual cancer subtypes have begun to identify key determinants of resistance, including up-regulation of multi-drug resistance (MDR) genes and mutational alterations of drug targets. However, these alterations are sufficient to explain only a minority of the population, and additional mechanisms of drug resistance or sensitivity are required to explain the remaining spectrum of patient responses to ultimately achieve the goal of precision oncology. We hypothesized that a pan-cancer analysis of in vitro drug sensitivities across numerous cancer lineages will improve the detection of statistical associations and yield more robust and, importantly, recurrent determinants of response. In this study, we developed a statistical framework based on the meta-analysis of expression profiles to identify pan-cancer markers and mechanisms of drug response. Using the Cancer Cell Line Encyclopaedia (CCLE), a large panel of several hundred cancer cell lines from numerous distinct lineages, we characterized both known and novel mechanisms of response to cytotoxic drugs including inhibitors of Topoisomerase 1 (TOP1; Topotecan, Irinotecan) and targeted therapies including inhibitors of histone deacetylases (HDAC; Panobinostat) and MAP/ERK kinases (MEK; PD-0325901, AZD6244). Notably, our analysis implicated reduced replication and transcriptional rates, as well as deficiency in DNA damage repair genes in resistance to TOP1 inhibitors. The constitutive activation of several signaling pathways including the interferon/STAT-1 pathway was implicated in resistance to the pan-HDAC inhibitor. Finally, a number of dysregulations upstream of MEK were identified as compensatory mechanisms of resistance to the MEK inhibitors. In comparison to alternative pan-cancer analysis strategies, our approach can better elucidate relevant drug response mechanisms. Moreover, the compendium of putative markers and mechanisms identified through our analysis can serve as a foundation for future studies into these drugs.

Several molecular epidemiological studies have been conducted to examine the association between glutathione S-transferase M 1 (GSTM1) null genotype and lung cancer in Asians; however, the conclusions remained controversial. We therefore performed an extensive meta-analysis on 31 published case-control studies with a total of 5347 lung cancer cases and 6072 controls.

Much evidence indicates that microRNAs could play potential roles as diagnostic and prognostic biomarkers of human cancers, including hepatocellular carcinoma (HCC). The present meta-analysis aimed to systematically evaluate the diagnostic accuracy of circulating microRNAs for HCC. Eligible studies were identified through multiple search strategies and assessed for relevance and quality. Results from different studies were pooled using random-effects models. The quality of each study was scored with the revised quality assessment of diagnostic accuracy studies tool. The summary receiver operator characteristic (SROC) curve and other measures were used to assess the overall performance of microRNA-based assays. Evidence of heterogeneity was evaluated using the I (2) test. Meta-regressions were conducted to analyze potential sources of heterogeneity. Deeks' test was used to test for potential publication bias. Thirty studies from 13 publications, including 1,314 patients with HCC and 1,407 controls, comprised healthy individuals and patients with hepatitis B/C or cirrhosis, were included in this meta-analysis. For diagnostic meta-analysis, the overall pooled results were as follows: sensitivity was 0.80 (95 % CI 0.74-0.84), specificity was 0.81 (95 % CI 0.74-0.87), positive likelihood ratio was 4.2 (95 % CI 3.0-6.0), negative likelihood ratio was 0.25 (95 % CI 0.19-0.38) and diagnostic odds ratio was 17 (95 % CI 10-29). The area under the SROC curve was 0.86 (95 % CI 0.84-0.90). Subgroup analyses suggested that multiple microRNAs had much better accuracy than single microRNA. Our findings suggest that circulating microRNAs show significant potential as diagnostic markers of HCC, particularly when using multiple microRNAs. However the results of this meta-analysis justify larger, more rigorous studies to confirm our conclusions.

To investigate the relationship of Apolipoprotein E (APOE) gene polymorphism to colorectal neoplasia (CRN), we performed a systematic review and meta-analysis. Eligible studies were identified through a systematic literature review from PubMed, EMBASE, and the Science Citation Index up to February 2014. A combined analysis was performed, followed by a subgroup analyses stratified by the study design. We used data collected from 8 prospective studies involving respectively a total of 9243 participants and 4310 CRN cases which including 438 patients with colorectal adenoma (CRA), and 3873 patients with colorectal carcinoma (CRC). The pooled data from this meta-analysis indicated there was no significant association between APOE polymorphism and CRN (ε2: P = 0.51, OR 1.04 95% CI 0.93 to 1.16; ε4: P = 0.72, OR 0.98 95% CI 0.90 to 1.07). Interestingly, subgroup analysis demonstrated there was a significant decreased risk for proximal CRN in patients with APOE ε4 (P = 0.0007, OR 0.52 95% CI 0.35 to 0.76). Data showed no significant association between APOE genotype and overall CRN. However, compared with those carry APOE ε3 alleles, persons with APOE ε4 genotype have significant decreased risk suffering from proximal CRN but not from distal CRN.

The detection of microRNAs (miRNAs), particularly those obtained from the bloodstream, is an emerging method for diagnosing human cancers, including non-small cell lung cancer (NSCLC). However, studies on the accuracy of miRNAs detection in diagnosing NSCLC have yield inconsistent conclusions, making it necessary to conduct a meta-analysis to systematically evaluate the diagnostic value of miRNAs in the diagnosis of NSCLC. The Medline, Embase, Chinese National Knowledge Infrastructure (CNKI), and Sinomed electronic databases were searched to identify all related articles evaluating the diagnostic value of miRNAs for NSCLC. A bivariate regression model was used to calculate the pooled diagnostic accuracy estimates. A total of 20 articles were included in this meta-analysis, involving 1,563 NSCLC patients and 1,060 healthy controls. Overall, our bivariate random effects meta-analysis yielded area under curve (AUC) of 0.85 (95 % CI: 0.82-0.88) with sensitivity of 76 % (95 CI: 72-80) and specificity of 80 % (95 % CI: 77-84) for the use of miRNAs in differentiating NSCLC patients from healthy controls. In addition, subgroup and meta-regression analyses revealed that a combination of multiple miRNAs (AUC, sensitivity, and specificity of 0.89, 81, and 84, respectively) had a higher diagnostic accuracy than single miRNA-based assays (AUC, sensitivity, and specificity of 0.81, 73, and 77 %, respectively). Furthermore, a comparison of miRNAs expression patterns between blood and sputum samples provides additional evidence that miRNAs obtained from blood (AUC, sensitivity, and specificity of 0.86, 78, and 80 %, respectively) are more credible diagnostic biomarkers than those from sputum (AUC, sensitivity, and specificity of 0.79, 66, and 79 %, respectively). In summary, the current meta-analysis suggests that the detection of miRNAs may be used in the future as an initial screening test for NSCLC, particularly, the detection of a combination of multiple miRNAs, which is a more comprehensive indicator than individual miRNAs.

Unique microRNAs (miRNAs) have been identified in colorectal cancer in recent studies which can be used to accurately diagnose the presence of colorectal cancer and help predict disease recurrence. Differential expression of specific miRNAs in tissues or blood offers the prospect of their use in early detection and screening for colorectal cancer. However, the experiments under different environments would produce different results. The purpose of this study was to get a reliable result on differentially expressed miRNAs related to colorectal cancer by integrating different studies.

Osteosarcoma is the most common primary bone malignancy in children and teenagers, and its clinical outcome remains poor. Previous studies have investigated the association between excision repair cross-complementing (ERCC) and prognosis of osteosarcoma patients, but their results were inconsistent. We aimed to clarify the associations between ERCC polymorphisms and osteosarcoma prognosis by using meta-analysis. We searched relevant studies in PubMed, Embase, coupled with Chinese National Knowledge Infrastructure (CNKI) in human osteosarcoma published prior to April, 2014. Hazard ratios (HR) together with their 95 % confidence intervals (95 % CI) were used to measure the relationship between ERCC mutations and prognosis in patients with osteosarcoma. Pooled results showed that polymorphism of ERCC2 Lys751Gln was associated with the overall survival of osteosarcoma (GG vs. AA, HR = 0.40; 95 % CI 0.18-0.86), and ERCC5 His46His mutation was associated with the event-free survival of osteosarcoma (CC vs. TT, HR = 0.37; 95 % CI 0.15, 0.93). In addition, there is no evidence of association on ERCC1 Asn118Asn, ERCC1 Gln504Lys, and ERCC2 Asp312Asn polymorphisms with prognosis in osteosarcoma. In summary, the ERCC2 Lys751Gln and ERCC5 His46His polymorphisms might influence osteosarcoma prognosis.

Cancer was viewed to be driven by accumulating genetic abnormalities that generally include chromosomal abnormalities, mutations in tumor-suppressor genes, and oncogenes. The aim of this meta-analysis was to systematically summarize the possible associations between MMP-13 rs2252070 A>G variant and cancer risks. We systematically reviewed studies focusing on MMP-13 polymorphisms with human cancer susceptibility that were published before April 30, 2014. Relevant articles were identified through research of PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases. All analyses were calculated using the Version 12.0 STATA software. Odds ratios (OR) and 95 % confidence interval (95 % CI) were calculated. Eleven independent case-control studies were included in the meta-analysis, which involved 3,465 patients with cancers and 4,073 healthy controls. The results identified a positive association between rs2252070 A>G polymorphism and susceptibility to cancer under five genetic models (all P < 0.05). Ethnicity subgroup analysis implied that significant difference was detected for rs2252070 A>G polymorphism with increased risk of cancers among Asians and Caucasians in majority of the groups. Our findings suggest significant association for MMP-13 rs2252070 A>G to increased susceptibility to human cancer, especially in the progression of lung carcinoma.

APE1 T1349G polymorphism was considered to be associated with risk of cancer, but studies on the association between APE1 T1349G polymorphism and risk of prostate cancer remained inconclusive. A meta-analysis of published studies was performed to precisely assess the association between APE1 Asp148Glu polymorphism and prostate cancer risk. PubMed, Embase, and Wanfang databases were searched for published case-control studies investigating the association between APE1 T1349G polymorphism and prostate cancer risk. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to assess the strength of the association. Overall, seven studies with a total of 3,063 individuals were finally included into the meta-analysis. The heterogeneity analysis did not find obvious heterogeneity among those included studies. Meta-analysis of total seven studies did not find an obvious association between APE1 T1349G polymorphism and prostate cancer risk (G vs T OR (95 % CI) = 1.11 (0.99-1.24); GG vs TT OR (95 % CI) = 1.25 (0.96-1.62); TG vs TT OR (95 % CI) = 1.11 (0.95-1.30); GG/TG vs T OR (95 % CI) = 1.13 (0.97-1.32); GG vs TT/TG OR (95 % CI) = 1.16 (0.91-1.48)). Subgroup analyses by ethnicity showed that APE1 T1349G polymorphism was associated with increased risk of prostate cancer in Caucasians (G vs T OR (95 % CI) = 1.26 (1.02-1.56), P = 0.033; TG vs TT OR (95 % CI) = 1.44 (1.06-1.94), P = 0.019; GG/TG vs T OR (95 % CI) = 1.45 (1.08-1.94), P = 0.013). The meta-analysis suggests that APE1 T1349G polymorphism is associated with increased risk of prostate cancer, especially in Caucasians. More studies are needed to further identify the obvious association above.

To uncover the genes involved in the development of osteosarcoma (OS), we performed a meta-analysis of OS microarray data to identify differentially expressed genes (DEGs) and biological functions associated with gene expression changes between OS and normal control (NC) tissues.

Recently, more and more studies investigated the value of microRNA (miRNA) as a diagnostic or prognostic biomarker in various cancers. MiR-21 was found dysregulated in almost all types of cancers. While the prognostic role of miR-21 in many cancers has been studied, the results were not consistent.

A number of studies have reported that HOTAIR expression levels were higher in cancerous tissues than in corresponding noncancerous tissues and overexpression of HOTAIR was prone to lymph node metastasis. This meta-analysis collected all relevant articles and explored the association between HOTAIR expression levels with lymph node metastasis. A literature collection was conducted by searching electronic databases PubMed, Cochrane Library, OVID, Web of Science, and CNKI (up to March 22, 2014). The odds ratio (OR) and its corresponding 95 % confidence interval (CI) were calculated to assess the strength of the association by using RevMan5.2 software. A total of 748 patients from 8 studies were included in this meta-analysis. The results showed there was a significant difference in the incidence of lymph node metastasis between high HOTAIR expression group and low HOTAIR expression group (OR = 2.81, 95 % CI 1.38-5.70, P = 0.004 random-effects model). This meta-analysis demonstrated that the incidence of lymph node metastasis in patients detected with high HOTAIR expression was higher than that in patients with low HOTAIR expression.