血浆游离DNA中黑色素瘤抗原A1基因启动子区甲基化在非小细胞肺癌诊断中的临床应用  

Preliminary study on methylation level of MAGE-A1 gene promoter in plasma cell-free DNA and its clinical application in the diagnosis of non-small cell lung cancer

作　　者：文韬 韩毅[1] 周世杰[1] 刘志东[1] WEN Tao;HAN Yi;ZHOU Shi-jie;LIU Zhi-dong(Department of Thoracic, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China)

机构地区：[1]首都医科大学附属北京胸科医院胸外科,北京101149

出　　处：《中国医刊》2019年第6期635-639,共5页Chinese Journal of Medicine

基　　金：北京市卫生系统高层次卫生技术人才培养项目(2014-3-081)

摘　　要：目的对血浆游离DNA中黑色素瘤抗原A1(melanoma antigen-A1,MAGE-A1)基因启动子区CpG岛甲基化水平进行初步检测,并探讨其对非小细胞肺癌(non-small cell lung cancer,NSCLC)的诊断价值。方法选取2017年3月至2018年6月首都医科大学附属北京胸科医院收治的经病理诊断确诊的NSCLC患者(研究组)56例,肺部良性病变患者(对照组)27例。应用甲基化敏感性限制性内切酶定量聚合酶链反应(methylation-sensitive restriction enzymes-based quantitative PCR,MSREqPCR)对两组患者血浆游离DNA中MAGE-A1基因启动子区CpG岛甲基化水平进行检测,并结合临床常用肿瘤标志物癌胚抗原(carcinoembryonic antigen,CEA)、血清骨胶素(CYFRA21-1)分析其在NSCLC诊断中的价值。结果研究组中MAGE-A1的甲基化水平明显低于对照组(P<0.05),其诊断NSCLC的敏感度和特异度分别为44.6%、88.9%,ROC曲线下面积(area under the curve,AUC)为0.691;在联合CEA和CYFRA211后其诊断敏感度和特异度可提升至67.9%、92.6%,AUC为0.844。结论游离DNA中MAGE-A1基因启动子区CpG岛甲基化水平对于NSCLC具有潜在的非侵入性辅助诊断价值。Objective To detect the methylation level of CpG island in the promoter region of melanoma antigen-A1 (MAGE-A1) gene in plasma cell-free DNA (cfDNA) and to explore its diagnostic value or non-small cell lung cancer (NSCLC). Method The methylation level of CpG island in the promoter region MAGE-A1 in cfDNA was detected by methylation-sensitive restriction enzymes-based quantitative PCR(MSRE-qPCR) in 56 patients with NSCLC and 27 patients with benign lung disease. At the same time, we compared CEA and CYFRA21-1 which were used as tumor markers in clinic with MAGE-A1, and analyzed their diagnostic value in NSCLC. Result The methylation level of MAGE-A1 in the NSCLC group was signifi cantly lower than that in the benign control group (P<0.05). The sensitivity, specifi city and the area under the ROC curve (AUC) of diagnosing NSCLC were 44.6%, 88.9% and 0.691, respectively. The sensitivity, specifi city and AUC could be improved to 67.9%, 92.6% and 0.844 when combined CEA and CYFRA21-1. Conclusion The methylation level of the promoter region of MAGE-A1 gene in cfDNA had potential value for the non-invasive diagnosis of NSCLC.

关 键 词：黑色素瘤抗原A1 游离DNA 甲基化 非小细胞肺癌 诊断 

分 类 号：R604[医药卫生—外科学]