Lin Zhenghua, Luo Mengzhao, Chen Xueqing, He Xingkang, Qian Yun, Lai Sanchuan, Si Jianmin, Chen Shujie
Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310020, Zhejiang Province, China.
Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang Province, China.
J Cancer. 2017 Apr 8;8(6):1038-1044. doi: 10.7150/jca.18169. eCollection 2017.
We try to explore the value of aberrant DNA methylation of several cancer-related genes in plasma as non-invasive biomarkers for gastric cancer (GC) and precancerous lesions. By using methylation-specific polymerase chain reaction assay we determined the methylation status of three selected genes , and in blood samples from patients with GC and precancerous lesions. We discovered that the methylation rate of , and increased significantly in the progression of gastric carcinogenesis. Methylation of was associated with positive serum CA19-9, while that of was related to H. pylori status, serum CA19-9 and CEA levels and tumor invasion depth. The Odds ratios (ORs) of , and methylation for predicting GC were 4.285 (95%CI: 2.435-7.542), 3.133 (95%CI: 1.700-5.775) and 2.674 (95%CI: 1.441-4.960), while for predicting "gastric cancer and intraepithelial neoplasia" (GnI), the ORs were 12.011 (95%CI: 0.050-28.564), 9.174 (95%CI: 3.220-26.135) and 12.794 (95%CI: 4.115-39.778), respectively. In terms of combined detection of these three genes, the sensitivity was 91.6% for GC and 89.8% for GnI, with the highest Youden index in both GC and GnI determination. Conclusively, combined detection of , and promoter hypermethylation might be a promising strategy for early detection of GC and precancerous lesions.
我们试图探索血浆中几种癌症相关基因的异常DNA甲基化作为胃癌（GC）及癌前病变的非侵入性生物标志物的价值。通过甲基化特异性聚合酶链反应分析，我们测定了GC患者和癌前病变患者血液样本中三个选定基因（此处原文未给出具体基因名称）的甲基化状态。我们发现，在胃癌发生发展过程中，这三个基因的甲基化率显著升高。其中一个基因的甲基化与血清CA19-9阳性相关，而另一个基因的甲基化与幽门螺杆菌感染状态、血清CA19-9和癌胚抗原水平以及肿瘤浸润深度有关。这三个基因甲基化预测GC的比值比（OR）分别为4.285（95%置信区间：2.435 - 7.542）、3.133（95%置信区间：1.700 - 5.775）和2.674（95%置信区间：1.441 - 4.960），而预测“胃癌和上皮内瘤变”（GnI）的OR分别为12.011（95%置信区间：0.050 - 28.564）、9.174（95%置信区间：3.220 - 26.135）和12.794（95%置信区间：4.115 - 39.778）。就这三个基因的联合检测而言，对GC的敏感性为91.6%，对GnI的敏感性为89.8%，在GC和GnI的测定中均具有最高的约登指数。总之，联合检测这三个基因的启动子高甲基化可能是早期检测GC和癌前病变的一种有前景的策略。
