老年肺癌患者血清RASSF1A基因启动子异常甲基化检测及其临床意义

The detection of aberrant methylation of RASSF1A promoter of serum DNA and its clinical significance in elderly lung cancer patients

目的探讨老年肺癌患者血清RASSF1A基因启动子区域的甲基化状态及其临床意义。方法采用甲基化特异性聚合酶链反应（MSP）技术，检测45例老年肺癌患者、20例肺部良性病变患者及15例健康志愿者血清RASSF1A基因启动子区域的甲基化状态，并分析其与临床病理参数之间的相关性。结果45例老年肺癌患者血清RASSF1A基因启动子区域异常甲基化15例，检出率为33．3％，而20例肺部良性疾病患者及15例健康志愿者中检出率均为0，差异有统计学意义（均为P〈0．01）。RASSF1A启动子异常甲基化在小细胞肺癌（SCLC）中有更高的检出率，但不同病理类型的非小细胞肺癌（NSCLC）异常甲基化的频率无明显差异。RASSF1A启动子异常甲基化与患者的性别、年龄、分化、分期和治疗干预无显著相关。结论RASSF1A启动子异常甲基化在老年肺癌患者血清中有着较高的检出率，可能成为肺癌诊断的分子标记。

Objective To detect the hypermethylation status of RASSF1A promoter in serum DNA of the elderly lung cancer patients and to analyze its correlation with clinical pathological features. Methods Serum DNA was extracted from peripheral blood of 45 primary lung cancer of elderly patients, 20 benign pulmonary disease patients and 15 healthy donors. The methylation status of RASSF1A promoter was determined using mthylation-specific polymerase chain reaction（PCR）, and the correlation between methylation profiles and clinical pathological parameters were statistically analyzed. Results Aberrant methylation of RASSF1A was detected in 15 of the 45（33.3%） cancer patients but in no benign pulmonary disease patients or healthy donors （P〈0. 001）. RASSF1A was preferentially observed in small cell lung cancer, while no statistical difference was found in methylation frequencies among different subtypes of non-small cell lung caner. The methylation status was also found to have no association with gender, age, differentiation, stage or treatment. Conclusions RASSF1 A promoter is frequently hypermethylated in serum DNA of primary lung cancer patients, and RASSF1A may be a novel biomarker for lung cancer diagnosis.