定量检测血浆RASSF1A甲基化在晚期肺癌患者个体化治疗中的应用

Application of quantitative detection of RASSF1A methylation in plasma for personalized chemotherapy of patients with advanced lung cancer

目的定量检测晚期肺癌患者化疗过程中血浆RAS相关区域家族1A基因(RASSF1A)甲基化水平,探讨其在个体化治疗中的应用价值。方法采集24例晚期肺癌患者化疗前后静脉血共135份,用荧光定量甲基化特异性PCR(MSP)检测RASSF1A基因的甲基化水平,观察化疗前后的变化情况。结果 13例部分缓解组(partial remission,PR)患者化疗后甲基化定量水平明显升高(P<0.05),而11例未缓解组(stable disease,SD或progressive disease,PD)的患者化疗前后甲基化水平无明显变化;生存时间≥12个月的13例患者化疗后甲基化定量水平也明显升高(P<0.01),而生存时间<12个月的11例患者化疗前后甲基化水平无明显变化。生存曲线分析显示,化疗后有甲基化水平升高改变的患者总体生存时间更长(P<0.01)。结论晚期肺癌患者化疗前后血浆RASSF1A甲基化定量水平的检测,对评估化疗的疗效及预后有一定的价值,对个体化化疗的药物选择有一定的指导意义。

Objective To quantitatively detect methylation level of Ras association domain family 1A gene（RASSF1A） in plasma of patients with advanced lung cancer and explore the application value in personalized chemotherapy.Methods A total of 135 blood samples were collected from 24 lung cancer patients before chemotherapy and after every therapeutic cycle.The methylation level of RASSF1A gene in plasma was detected by real-time methylation specific PCR,and the changes of methylation level before and after chemotherapy were analyzed.Results The RASSF1A methylation levels of 13 partial remission（PR） patients after the first cycle of chemotherapy were statistically elevated（P0.05）,but not significantly elevated in 11 non-remission patients in either stable or progressive stage.RASSF1A methylation levels of 13 cases whose survival time were more than or equal to 12 months after the first cycle of chemotherapy were statistically elevated（P0.01）.However,the RASSF1A methylation levels were not significantly elevated in 11 cases with the survival time of less than 12 months.Survival curve analysis showed a statistically longer survival time in patients who had elevated methylation level in plasma DNA after the first cycle of chemotherapy（P0.01）.Conclusions The quantitation of RASSF1A gene methylation in plasma DNA is a sensitive indicator of effective chemotherapy and suggest better prognosis,and may be useful for choosing personalized chemotherapy drugs for the patients with advanced lung cancer.