Department of Biochemistry, University of Kashmir, Srinagar, India.
Department of Gastroenterology, Government Medical College and Hospital, Srinagar, India.
Mol Biol Rep. 2021 Jan;48(1):405-412. doi: 10.1007/s11033-020-06064-4. Epub 2021 Jan 4.
Gastric cancer (GC) is a multistep process characterized by a gradual accumulation of genetic and epigenetic alterations in genes at various stages of progression. Epigenetic alterations like DNA methylation play an important role in cancer and may serve as a biomarker for cancer. The present study was aimed to investigate the promoter hypermethylation, expression profile, and Arg399Gln gene polymorphism of DNA repair gene XRCC1 (X-ray repair cross complimentary group I) in GC patients. A total of 60 histopathologically confirmed GC subjects were recruited in the study. Information on various dietary, lifestyle and environmental factors was obtained in face-to-face interviews using a structured questionnaire from each subject. Tissue samples were taken along with adjacent non-cancerous tissues for analysis. Promoter methylation status and expression of XRCC1 gene was evaluated using MS-PCR and western blotting respectively; while as Arg399Gln polymorphism was analyzed by PCR-RFLP. We found that the XRCC1 gene promoter of 38.3% cancerous tissues were methylated compared to 13.3% of adjacent normal tissues. The promoter hypermethylation status of the gene was found to be significantly associated with the loss of protein expression (P < 0.0001, OR = 14.63; 95% CI 4.01-53.43). However, we did not find any significant association of polymorphism of XRCC1 Arg399Gln with promoter methylation or protein expression. Further, comparison of methylation status and protein expression with clinical parameters like age, smoking status, etc. was also not significant (P > 0.05). The present study indicates that XRCC1 undergoes aberrant promoter hypermethylation with subsequent loss of protein expression in gastric cancer.
胃癌（GC）是一个多步骤的过程，其特征是在不同进展阶段的基因中逐渐积累遗传和表观遗传改变。表观遗传改变，如 DNA 甲基化，在癌症中起着重要作用，并且可以作为癌症的生物标志物。本研究旨在调查 DNA 修复基因 XRCC1（X 射线修复交叉互补组 I）在胃癌患者中的启动子高甲基化、表达谱和 Arg399Gln 基因多态性。共招募了 60 例经组织病理学证实的 GC 患者。通过对每位患者进行面对面访谈，使用结构化问卷获得有关各种饮食、生活方式和环境因素的信息。从每个患者中采集组织样本和相邻的非癌组织进行分析。使用 MS-PCR 和 Western blot 分别评估 XRCC1 基因启动子甲基化状态和表达；而 Arg399Gln 多态性则通过 PCR-RFLP 进行分析。我们发现，与 13.3%的相邻正常组织相比，38.3%的癌组织中 XRCC1 基因启动子发生了甲基化。该基因启动子的高甲基化状态与蛋白表达的丧失显著相关（P <0.0001，OR=14.63；95%CI 4.01-53.43）。然而，我们没有发现 XRCC1 Arg399Gln 多态性与启动子甲基化或蛋白表达之间存在任何显著关联。此外，与临床参数（如年龄、吸烟状况等）相比，对甲基化状态和蛋白表达的比较也没有显著差异（P>0.05）。本研究表明，XRCC1 在胃癌中发生异常启动子高甲基化，随后蛋白表达丧失。
