XRCC1基因的DNA甲基化在胃癌患者铂类药物化疗疗效中的预测作用

XRCC1 gene DNA methylation on predicting the efficacy of oxaliplatin-based chemotherapy in patients with gastric cancer

摘要:

目的： 探讨XRCC1基因的DNA甲基化对接受含奥沙利铂方案辅助化疗胃癌患者的疗效预测价值。方法： 经病理确诊的胃癌患者116例，接受奥沙利铂和氟尿嘧啶类联合的方案化疗至少6周期。采用亚硫酸氢盐测序法对胃癌手术标本进行XRCC1基因的甲基化水平检测，并分析其与胃癌患者化疗疗效的相关性。结果： 不同性别、年龄、是否淋巴结转移、不同肿瘤直径、不同分化程度、是否接受辅助化疗的胃癌患者之间XRCC1基因的DNA甲基化水平差异均无统计学意义（P>0.05）。术后接受化疗和未接受化疗的胃癌患者的平均生存期分别为（42.82±3.57）个月和（25.68±4.90）个月，接受化疗的胃癌患者生存期更长（χ²=7.208，P=0.07）。化疗有效组的平均甲基化率为51.60%，化疗无效组为38.31%，2组比较差异具有统计学意义（P<0.05）。结论： XRCC1基因的DNA甲基化率与奥沙利铂的敏感性呈正相关，是潜在的预测胃癌患者化疗有效性及预后的分子标记物。

Abstract:

Objective: To investigate the value of XRCC1 gene DNA methylation in predicting the efficacy of oxaliplatin-based adjuvant chemotherapy in patients with gastric cancer. Methods: A total of 116 patients with gastric cancer received at least 6 cycles of combination chemotherapy of oxaliplatin and fluorouracil. Bisulfite sequencing was used to analyze the methylation of XRCC1 gene in gastric cancer surgical specimens, and the correlation with the efficacy of chemotherapy in patients with gastric cancer were also analyzed. Results: There was no statistically significant difference in the average methylation rates of XRCC1 gene among gastric cancer patients with different gender, age, lymph node metastasis, tumor diameters, differentiation, and whether they received adjuvant chemotherapy (P>0.05) . The average survival time of gastric cancer patients receiving chemotherapy and not receiving chemotherapy were (42.82±3.57) months and (25.68±4.90) months, respectively. The survival time of gastric cancer patients receiving chemotherapy was longer (χ²=7.208, P=0.007) . The average methylation rate of chemotherapy effective group was 51.60%, and that of chemotherapy ineffective group was 38.31%, with significant differences between the two groups (P<0.05) . Conclusion: The DNA methylation rate of XRCC1 gene is positively correlated with the sensitivity of oxaliplatin, which is a potential molecular marker to predict the efficacy and prognosis of chemotherapy in patients with gastric cancer.