Efficient isolation and proteomic analysis of cell plasma membrane proteins in gastric cancer reveal a novel differentiation and progression related cell surface marker, R-cadherin.

Cell plasma membrane proteins, playing a crucial role in cell malignant transformation and development, were the main targets of tumor detection and therapy. In this study, CyDye/biotin double-labeling proteomic approach was adopted to profile the membrane proteome of gastric cancer cell line BGC-823 and paired immortalized gastric epithelial cell GES-1. Real-time PCR, Western blotting, and immunohistochemical staining were used to validate the differential expression of a novel identified cell surface marker R-cadherin in gastric cancer cells and tissues. Clinicopathological study and survival analysis were performed to estimate its roles in tumor progression and outcome prediction. Real-time PCR and Western blotting showed that the expression level of R-cadherin in gastric cancer were significantly lower than non-cancerous epithelial cell and tissues. Clinicopathological study indicated that R-cadherin was dominantly expressed on cell surface of normal gastric epithelium, and its expression deletion in gastric cancer tissues was associated with tumor site, differentiation, lymph node metastasis, and pTNM (chi-square test, P < 0.05). Those patients with R-cadherin positive expression displayed better overall survivals than negative expression group (log-rank test, P = 0.000). Cox multivariate survival analysis revealed lacking the expression of R-cadherin was a main independent predictor for poor clinical outcome in gastric cancer (RR = 5.680, 95 % CI 2.250-14.341, P < 0.01). We have established a fundamental membrane proteome database for gastric cancer and identified R-cadherin as a tumor differentiation and progression-related cell surface marker of gastric cancer. Lacking the expression of R-cadherin indicates poor prognosis in patients with gastric cancer.

Correlation Between Interleukin-1ß-511 C/T Polymorphism and Gastric Cancer in Chinese Populations: A Meta-Analysis.

BACKGROUND Several studies have indicated that interleukin (IL)-1ß-511 C/T polymorphism may contribute to individual susceptibility to gastric cancer, but the results vary among regions and races. No relevant meta-analysis has been conducted in a Chinese population. Therefore, we performed the current meta-analysis to investigate the possible correlation between IL-1ß-511 C/T polymorphism and gastric cancer susceptibility in Chinese subjects. MATERIAL AND METHODS PubMed, EmBase, Cochrane Library, Chinese Biology Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases were searched for case-control studies published before 21 January 2015 and investigating a correlation between IL-1ß-511 C/T polymorphism and gastric cancer susceptibility. Two investigators independently screened the studies, extracted data, and evaluated the quality of included studies with the Newcastle-Ottawa scale. Meta-analysis was conducted with STATA 12.0. RESULTS A total of 27 articles from 28 case-control studies were collected. Meta-analysis showed that IL-1ß-511C/T polymorphism was related to increased susceptibility to gastric cancer in Chinese subjects [T vs. C: OR=1.21, 95%CI (1.07-1.37), P<0.01; TT vs. CC: OR=1.41, 95%CI (1.11-1.80), P<0.01; CT vs. CC: OR=1.26, 95% CI (1.05-1.50), P<0.01; TT+CT vs. CC: OR=1.31, 95%CI (1.08-1.58), P<0.01; and TT vs. CT+CC: OR=1.24, 95%CI (1.05-1.47), P<0.01]. Subgroup analysis showed a significant correlation between IL-1ß-511C/T polymorphism and susceptibility to gastric cancer in residents of southern China and in patients with intestinal-type gastric cancer, but not in residents of northern China or in patients with diffuse gastric cancer. Moreover, H. pylori-infected subjects carrying T (CT+TT) exhibited a relatively higher risk of GC [OR=2.4, 95% CI (1.2-5.1), P=0.02]. CONCLUSIONS IL-1ß-511C/T polymorphism is significantly associated with increased susceptibility to gastric cancer in residents of southern China and in intestinal-type gastric cancer. We also found a synergistic interaction between IL-1ß-511C/T polymorphism and H. pylori infection in the development of GC.

Roles of Cyclooxygenase-2 gene -765G > C (rs20417) and -1195G > A (rs689466) polymorphisms in gastric cancer: A systematic review and meta-analysis.

BACKGROUND: The roles of cyclooxygenase-2 (COX2) -765G > C (rs20417) and -1195G > A (rs689466) polymorphisms in gastric cancer were intensively analyzed, but the results of these studies were inconsistent. We conducted a meta-analysis and trial sequential analysis to elucidate the associations between these two COX2 polymorphisms and gastric cancer risk. METHODS: Eligible studies were searched in PubMed, Embase, Cochrane library databases, China National Knowledge Infrastructure, Vip, and Wanfang databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the genetic correlation between COX2 polymorphisms and gastric cancer susceptibility in five genetic models. Trial sequential analysis (TSA) was conducted to estimate whether the evidence of the results is sufficient. Furthermore, their interactions with Helicobacter pylori (H. pylori) or smoking in gastric cancer were also assessed using a case-only method. RESULTS: The COX2 gene -765G > C polymorphism showed no significant association with gastric cancer susceptibility under all the five genetic models (take the allelic model for example: OR = 1.41, 95% CI: 0.95-2.09) in total analysis, and the stratification analysis by ethnicity indicated a similar association in Caucasian group under four genetic models (allelic model, dominant model, homozygous model, and heterozygous model). But in the subgroup of the Asian population, the -765G > C polymorphism was significantly associated with gastric cancer risk under the same contrast. The COX2 -1195G > A polymorphism showed significant correlation with gastric cancer susceptibility in total analysis, and stratification analysis by ethnicity also revealed a similar association in both Asian and Caucasian groups under the same contrast. Moreover, TSA confirmed such associations. Both H. pylori infection and cigarette smoking interacted with -765 C allele in gastric cancer (OR = 3.79, 95% CI: 1.15-12.43 and OR = 2.48, 95% CI: 1.38-4.48, respectively), but not in -1195 A allele (OR = 1.96, 95% CI: 0.62-6.21, and OR = 1.24, 95% CI: 0.93-1.64, respectively). CONCLUSIONS: COX2 -765G > C polymorphism may serve as a genetic biomarker of gastric cancer in Asians, but not in Caucasians. COX2 -1195G > A polymorphism may serve as a genetic biomarker of gastric cancer in both Asians and Caucasians. The -765G > C, rather than -1195G > A polymorphism interacted with H. pylori infection or cigarette smoking to increase gastric cancer risk.