Department of Health Management, Weifang People's Hospital, Weifang, Shandong, China (mainland).
Department of Radiotherapy, Weifang People's Hospital, Weifang, Shandong, China (mainland).
Med Sci Monit. 2017 Nov 12;23:5389-5395. doi: 10.12659/msm.903927.
BACKGROUND The purpose of this study was to investigate the prognostic significance of methylation of RAS association domain family protein 1 (RASSF1A) in the promoter region for patients with stage II and III colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy. MATERIAL AND METHODS There were 108 eligible CRC patients and 78 healthy controls included in this study. Methylation-specific polymerase chain reaction (MSP) was applied to detect the methylation status of RASSF1A in patients before and after chemotherapy. The effects of RASSF1A methylation on chemotherapy-sensitivity and prognosis for patients were also evaluated in the present study. RESULTS The frequency of RASSF1A methylation was higher in CRC patients than in the healthy controls (48.44% versus 5.13%, p<0.001). After two cycles of chemotherapy, methylation ratio was significantly decreased (21.30%, p<0.001). Promoter methylation of RASSF1A was significantly correlated with tumor stage and pathological differentiation (p=0.008 and p=0.007, respectively). Patients without methylation had a favorable objective response (OR), compared with those with methylation (53.33% versus 25%, p=0.014). Methylation status of RASSF1A could influence progression-free survival and overall survival (log rank test, p<0.05). Cox regression analysis indicated that RASSF1A methylation (HR=2.471, 95% CI=1.125-5.428, p=0.024) and OR (HR=2.678, 95% CI=1.085-6.610, p 0.033) were independently correlated with prognosis for patients treated with oxaliplatin-based chemotherapy. CONCLUSIONS Promoter methylation of RASSF1A can influence sensitivity to oxaliplatin-based chemotherapy, which can be used to predict outcomes for patients with stage II and III CRC. In addition, the aberrant methylation may be a promising target for improving chemotherapy efficacy.
本研究旨在探讨 RAS 相关结构域家族蛋白 1（RASSF1A）启动子区甲基化在接受奥沙利铂为基础化疗的 II 期和 III 期结直肠癌（CRC）患者中的预后意义。
本研究纳入了 108 例符合条件的 CRC 患者和 78 例健康对照者。采用甲基化特异性聚合酶链反应（MSP）检测患者化疗前后 RASSF1A 的甲基化状态。还评估了 RASSF1A 甲基化对患者化疗敏感性和预后的影响。
CRC 患者的 RASSF1A 甲基化频率高于健康对照者（48.44%比 5.13%，p<0.001）。化疗 2 个周期后，甲基化率显著降低（21.30%，p<0.001）。RASSF1A 启动子甲基化与肿瘤分期和病理分化显著相关（p=0.008 和 p=0.007）。无甲基化的患者客观缓解率（OR）优于有甲基化的患者（53.33%比 25%，p=0.014）。RASSF1A 甲基化状态可影响无进展生存期和总生存期（log rank 检验，p<0.05）。Cox 回归分析表明，RASSF1A 甲基化（HR=2.471，95%CI=1.125-5.428，p=0.024）和 OR（HR=2.678，95%CI=1.085-6.610，p=0.033）与接受奥沙利铂为基础化疗的患者的预后独立相关。
RASSF1A 启动子甲基化可影响奥沙利铂为基础化疗的敏感性，可用于预测 II 期和 III 期 CRC 患者的预后。此外，异常甲基化可能是提高化疗疗效的一个有前途的靶点。
