Yang Zhiping, Qi Weibo, Sun Li, Zhou Hui, Zhou Biliu, Hu Yi
Department of Oncology, The First Affiliated Hospital of Jiaxing University, Zhejiang, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Jiaxing University, Zhejiang, China.
Adv Clin Exp Med. 2019 Mar;28(3):355-360. doi: 10.17219/acem/84935.
Lung cancer is still the deadliest cancer in the world, but early diagnosis cannot be achieved because of the limitations of diagnostic methods. DNA methylation has been proven to be a potentially powerful tool for cancer detection and diagnosis over the past decade.
We explored whether free DNA methylation in plasma can be a reliable biomarker for noninvasive lung cancer detection.
We detected the methylation of 8 genes in plasma-free DNA of patients with pulmonary space-occupying lesions using real-time quantitative methylation-specific polymerase chain reaction (QMSP). Among the 50 selected patients, 39 were confirmed using pathological analysis as having early lung cancer and 11 had an inflammatory pseudotumor.
The QMSP detection showed that the methylation levels of 8 genes in the patients were significantly higher than in the non-lung cancer group. The methylation level of CALCA was the highest and the methylation level of HOXA9 was the lowest. Methylation of RASSF1A, CDKN2A and DLEC1 occured only in lung cancer patients, while methylation of CALCA, CDH13, PITX2, HOXA9, and WT1 occured not only in lung cancer patients, but also in non-lung cancers. The specificity reached 95~100%, whether for a single gene or overall, but the sensitivity was relatively low for each gene. The sensitivity can reach 72% if the methylation of any of the 8 genes is positive and the overall specificity was 91%. The positive and negative predictive values were 96% and 60%, respectively.
Quantitative detection of DNA methylation in plasma is a potential method for early diagnosis of lung cancer.
肺癌仍是全球致死率最高的癌症，但由于诊断方法的局限性，无法实现早期诊断。在过去十年中，DNA甲基化已被证明是一种潜在的强大癌症检测和诊断工具。
我们探讨血浆中游离DNA甲基化是否可作为非侵入性肺癌检测的可靠生物标志物。
我们采用实时定量甲基化特异性聚合酶链反应（QMSP）检测肺占位性病变患者血浆游离DNA中8个基因的甲基化情况。在选取的50例患者中，39例经病理分析确诊为早期肺癌，11例患有炎性假瘤。
QMSP检测显示，患者中8个基因的甲基化水平显著高于非肺癌组。CALCA的甲基化水平最高，HOXA9的甲基化水平最低。RASSF1A、CDKN2A和DLEC1的甲基化仅发生在肺癌患者中，而CALCA、CDH13、PITX2、HOXA9和WT1的甲基化不仅发生在肺癌患者中，也发生在非肺癌患者中。无论是单个基因还是整体，特异性均达到95%至100%，但每个基因的敏感性相对较低。如果8个基因中的任何一个甲基化呈阳性，敏感性可达到72%，总体特异性为91%。阳性和阴性预测值分别为96%和60%。
血浆DNA甲基化定量检测是肺癌早期诊断的一种潜在方法。
