Detecting promoter methylation pattern of apoptotic genes Apaf1 and Caspase8 in gastric carcinoma patients undergoing chemotherapy

检测接受化疗的胃癌患者中凋亡基因Apaf1和Caspase8启动子甲基化模式

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Abstract

BACKGROUND: DNA methylation patterns in cells dysregulation CpG island methylation of genes involved in cancer leads to increased levels of the cancer. Restoration of the apoptotic route in tumor cells of stomach in order for placing Casp8 and Apaf1 genes is a proper approach for new treatments of gastric cancer. The objective of the present study was to investigate the relationship between the pattern of methylation promoter in apoptotic genes of Casp8 and Apaf1 and gastric carcinoma in patients receiving chemotherapy. METHODS: Genomic DNA was extracted from 30 samples of FFPE tumor, normal tissues and blood samples. Hyper-methylation analysis of Casp8 and Apaf1 genes was conducted using MSP method; the results were analyzed through electrophoresis on agarose gel and software spss20. RESULTS: In this study, methylation rate of Apaf1 gene with (P>0.05) was not significant but methylation rate of Casp8 gene with (P<0.05) was significant. In addition, there was a significant relationship between Apaf1 gene methylation in blood with stage (P<0.05), Apaf1 gene methylation in tissue with stage (P<0.05) and grade (P<0.01) and between Casp8 gene methylation in blood with age (P<0.001) of patients but no significant relationship was seen for other factors. CONCLUSIONS: Our results suggest that epigenetic mechanisms play an important role in the pathogenesis of gastric cancer and can be utilized as prognostic biomarkers for it. Also no significant difference between Casp8 and Apaf1 promoter hypermethylation in blood and tissue samples indicated that methylation status of blood sample can be early and non-invasive diagnostic marker in gastric cancer.

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