Study On The Correlation Between RUNX3,RASSF1A Promoter Hypermethylation With The Progress And Metastasis Of Gastric Carcinoma

BackgroundGastric cancer is one of the most malignancies cancers in the word, the five-year survival rates of GC is less than 20%,whether occurring metastasis will impact the treatment selection and prognosis. Aberrant methylation in the promoter is associated with the reduced expression of tumor suppressor genes, and is the major mechanism for the development of gastric cancer.However,the role of the hypermethylation of the tumor suppressor gene in gastric cancer progression and metastasis is not fully understood. RUNT related gene 3(RUNX3)and RAS association domain familiy 1A (RASSF1A)were both found to be lost or reduced expression in gastric cancer,while the gene mutation was rare to be found.ObjectiveThis study was to detect the implications of promoter methylation of RUNX3 and RASSF1A genes in the tissues of gastric cancer and to explore the relationship among the promoter methylation of RUNX3, RASSF1A, the mRNA expression and the progress,metastasis of gastric cancer characters.MethodsRT-PCR and MSP were used to detect the mRNA expression and methylation of RUNX3, RASSF1A genes from 62 cases of gastric cancer specimens with 56 cases of adjacent normal tissues. Protein expression of VEGF was measured by immunohistochemistry in methylated and unmethylated cancer tissues and 20 normal gastric tissues. P value<0.05 was considered significantly in all statistical analysis.ResultsThe mRNA expression of RUNX3 (0.629±0.461 vs 0.893±0.543) and RASSF1A (0.653±0.476 vs 0.858±0.581) were significantly reduced in GC compared to the normal tissue.The methylation rates of RUNX3 and RASSF1A in gastric cancer tissues (69.4% and 66.1%) were signifiantly higher than that in normal tissues (26.8 % and 23.2%). RUNX3 and RASSF1A in methylation group of GC were reduced compared to the unmethylation group of GC(RUNX3: 0.545±0.299 vs 0.736±0.291, RASSF1A: 0.562±0.208 vs 0.674±0.185, P<0.05, respectively). RUNX3 and RASSF1A methylation were both not related with sex, age, tumor size, tumor differentiation grade, Lauren classification. But RASSF1A methylation were related with pTNM stages and depth of infiltration. RUNX3 methylation was related with lymph node metastasis,vascular invasion and pTNM stages. VEGF protein expression was significantly higher in methylated GC compared to the unmethylated GC (86.0% vs 57.9%, P<0.05).ConclusionAberrant methylation in the promoter of RUNX3,RASSF1A may be serve as a cause of losing the expression of the genes, and was involved in the progressing of GC. Methylation of RUNX3 might participate in vascular/lymphatic metastasis of GC. By detecting the methylaiton of RUNX3 and RASSF1A genes could contribute to an accurate assessment of the classification, and to determine metastases of GC. Application of drugs to reverse the methylation of RUNX3 gene methylation perhaps could reduce the vascular and lymphatic angiogenesis by reducing VEGF expression in gastric carcinoma, but still needs further study.