Relationships between abnormal MMP2 expression and prognosis in gastric cancer: a meta-analysis of cohort studies.

We carried out this current meta-analysis of relevant cohort studies in an attempt to investigate the relationships between abnormal matrix metalloproteinases-2 (MMP2) expression and gastric cancer (GC) prognosis. A range of electronic databases were searched for relevant articles without any language restrictions: Web of Science (1945-2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966-2013), EMBASE (1980-2013), CINAHL (1982-2013), and the Chinese Biomedical Database (CBM) (1982-2013). Meta-analysis was conducted using the STATA 12.0 software. Crude hazard ratios (HRs), with 95% confidence intervals (95% CIs), were calculated. Ten clinical cohort studies with a total of 1669 GC patients were included in this meta-analysis. The results of our meta-analysis suggested that MMP2-positive patients display a shorter overall survival (OS) than MMP2-negative patients (HR=1.31, 95% CI=0.98-1.63, p<0.001). Subgroup analysis based on ethnicity revealed that abnormal MMP2 expression was associated with significantly worse OS in patients with GC among both Caucasian and Asian populations (all p<0.05). Our meta-analysis indicated that abnormal MMP2 expression may be strongly correlated with poor prognosis in patients with GC. Thus, MMP2 expression may serve as an independent prognostic factor for GC.

Abnormal FHIT protein expression may be correlated with poor prognosis in gastric cancer: a meta-analysis.

Our current meta-analysis is aimed to investigate the relationships between fragile histidine triad (FHIT) protein expression and prognosis in gastric cancer patients. We searched MEDLINE (1966 ~ 2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of Science (1945 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013) without any language restrictions. The meta-analysis was conducted using the STATA 12.0 software. Crude hazard ratios (HR) with its 95 % confidence interval (95 % CI) were calculated. Eight clinical cohort studies with a total of 1,361 gastric cancer patients were involved in our meta-analysis. Our results revealed that FHIT-negative patients exhibited a shorter overall survival (OS) time than FHIT-positive patients (HR = 1.23, 95 % CI = 1.01 ~ 1.44, P < 0.001). Ethnicity-stratified analysis demonstrated that FHIT-negative patients have significantly poorer prognosis than FHIT-positive patients among both Caucasians and Asians (all P < 0.05). In conclusion, our meta-analysis provides evidences that negative expression of FHIT protein may be correlated with poor prognosis in patients with gastric cancer. Thus, FHIT expression level may be utilized as an independent prognostic marker for gastric cancer.

Promoter methylation of the RASSF1A gene may contribute to colorectal cancer susceptibility: a meta-analysis of cohort studies.

This meta-analysis of published cohort studies was conducted to evaluate whether promoter methylation of the RASSF1A gene contributes to colorectal cancer (CRC) susceptibility. A range of electronic databases were searched without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude risk differences (RD) with their 95% confidence intervals (95%CI) were calculated. In this meta-analysis, 11 clinical cohort studies with a total of 630 CRC patients were included. The pooled results revealed that the frequency of RASSF1A gene methylation in cancer tissues was significantly higher than that in benign, adjacent, and normal tissues (cancer tissues vs. benign tissues: RD = 0.25, 95%CI = 0.13-0.38, P < 0.001; cancer tissues vs. adjacent tissues: RD = 0.32, 95%CI: 0.20-0.45, P < 0.001; cancer tissues vs. normal tissues: RD = 0.38, 95%CI: 0.26-0.50, P < 0.001; respectively). Subgroup analysis by ethnicity demonstrated that RASSF1A promoter methylation also exhibited a higher frequency in cancer tissues among both Asians and Caucasians (all P < 0.05). Our meta-analysis has shown positive correlations between RASSF1A promoter methylation and CRC susceptibility. Thus, detection of RASSF1A promoter methylation may be utilized as a valuable diagnostic marker for CRC.

ALDH2 and ADH1 genetic polymorphisms may contribute to the risk of gastric cancer: a meta-analysis.

AIM: We conducted a meta-analysis of case-control studies to determine whether ALDH2, ADH1 and ADH2 genetic polymorphisms contribute to the pathogenesis of gastric cancer. METHODS: The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before November 1st, 2013 without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. We calculated crude odds ratios (ORs) with their 95% confidence intervals (95%CI) to evaluate their relationships under five genetic models. Seven case-control studies with a total of 2,563 gastric cancer patients and 4,192 healthy controls met the inclusion criteria. Nine common polymorphisms were evaluated, including rs671, rs16941667 and rs886205 in the ALDH2 gene, rs1230025, rs13123099, rs698 and rs1693482 in the ADH1 gene, and rs1229984 and rs17033 in the ADH2 gene. RESULTS: The results of our meta-analysis suggested that ALDH2 genetic polymorphisms might be strongly correlated with an increased risk of gastric cancer (allele model: OR = 1.21, 95%CI: 1.11 ∼ 1.32, P<0.001; dominant model: OR = 1.23, 95%CI: 1.09 ∼ 1.39, P = 0.001; respectively), especially for rs671 polymorphism. Furthermore, we observed significant associations between ADH1 genetic polymorphisms and an increased risk of gastric cancer (allele model: OR = 1.21, 95%CI: 1.08 ∼ 1.36, P = 0.001; dominant model: OR = 10.52, 95%CI: 3.04 ∼ 36.41, P<0.001; respectively), especially for rs1230025 polymorphism. Nevertheless, no positive relationships were found between ADH2 genetic polymorphisms and gastric cancer risk (all P>0.05). CONCLUSION: The current meta-analysis suggests that ALDH2 and ADH1 genetic polymorphisms may play crucial roles in the pathogenesis of gastric cancer. However, ADH2 genetic polymorphisms may not be important dominants of susceptibility to gastric cancer.

Role of p16 gene promoter methylation in gastric carcinogenesis: a meta-analysis.

This meta-analysis was performed to evaluate the relationships between promoter DNA methylation in tumor suppressor gene p16 and gastric carcinogenesis. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library and CBM databases were searched for relevant articles published before November 1st, 2013 without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated. Forty-seven clinical cohort studies that met all inclusion criteria were included in this meta-analysis. A total of 2,813 gastric cancer (GC) patients were assessed. Our meta-analysis results revealed that the frequencies of p16 promoter methylation in the GC tissues were higher than those of normal and adjacent tissues (Normal: OR = 23.04, 95% CI = 13.55-39.15, P < 0.001; Adjacent: OR = 4.42, 95% CI = 1.66-11.76, P = 0.003; respectively). Furthermore, we observed significant associations of p16 promoter methylation with TNM stage, histologic grade, invasive grade, lymph node metastasis of GC (TNM stage: OR = 3.60, 95% CI: 2.17-5.98, P < 0.001; Histologic grade: OR = 2.63, 95% CI: 1.55-4.45, P < 0.001; Invasive grade: OR = 3.44, 95% CI: 1.68-7.06, P = 0.001; Lymph node metastasis: OR = 2.68, 95% CI: 1.66-4.32, P < 0.001; respectively). However, there were no correlations of p16 promoter methylation with the TNM stage and Helicobacter pylori (HP) infection of GC (Tumor size: OR = 0.76, 95% CI: 0.14-4.07, P = 0.746; HP infection: OR = 1.31, 95% CI: 0.75-2.27, P = 0.342; respectively). Our findings provide empirical evidence that p16 promoter methylation may play an important role in gastric carcinogenesis. Thus, p16 promoter methylation may be a promising potential biomarker for the early diagnosis of GC.

Aberrant promoter methylation of RASSF1A gene may be correlated with colorectal carcinogenesis: a meta-analysis.

We conducted a meta-analysis of cohort studies to evaluate the potential role of RASSF1A promoter methylation in colorectal carcinogenesis. A range of electronic databases were searched: PubMed (1966-2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and the Chinese Biomedical Database (CBM) (1982-2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratio (OR) with 95% confidence interval (95% CI) was calculated. Eleven clinical cohort studies with a total of 1,505 colorectal cancer (CRC) patients that met all inclusion criteria were included in our meta-analysis. The results of our meta-analysis revealed that the frequency of RASSF1A promoter methylation was strongly correlated with clinical stage (OR = 1.69, 95% CI 1.16-2.44, P = 0.006), histological grade (OR = 1.92, 95% CI 1.22-3.04, P = 0.005) and distant metastasis (OR = 2.59, 95% CI 1.46-4.60, P = 0.037) of CRC patients. However, we observed no positive correlations of RASSF1A promoter methylation with gender (OR = 1.04, 95% CI 0.74-1.46, P = 0.842), age (OR = 1.70, 95% CI 0.98-2.93, P = 0.057) and lymph node metastasis (OR = 1.65, 95% CI 0.87-3.14, P = 0.127) of CRC patients. Further subgroup analysis by ethnicity demonstrated that RASSF1A promoter methylation was correlated with clinicopathological characteristics of CRC patients among Asians (clinical stage: OR = 2.55, 95% CI 1.55-4.20, P < 0.001; histological grade: OR = 2.70, 95% CI 1.44-5.06, P = 0.002; lymph node metastasis: OR = 4.09, 95% CI 1.49-11.26, P = 0.006; distant metastasis: OR = 5.38, 95% CI 1.73-16.70, P = 0.004), but not among Caucasians and Africans (all P > 0.05). Our meta-analysis has shown positive correlations between aberrant promoter methylation of RASSF1A gene and clinicopathological characteristics of CRC patients, especially among Asians.