Hu Sifeng, Yin Xiankun, Zhang Guangyong, Meng Fanmei
Department of General Surgery, Zoucheng People's Hospital, Zoucheng, Shandong, People's Republic of China.
Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
J Cell Biochem. 2019 Jul;120(7):11708-11715. doi: 10.1002/jcb.28450. Epub 2019 Feb 18.
Gastric adenocarcinoma is an important death-related cancer. To find factors related to survival and prognosis, and thus improve recovery prospects, a powerful signature is needed. DNA methylation plays an important role in gastric adenocarcinoma processes and development, and here we report on the search for a significant DNA methylation gene to aid with the earlier diagnosis of gastric adenocarcinoma patients. A Cox proportional risk regression analysis and random survival forest algorithm were used to analyze gastric adenocarcinoma patients' DNA methylation data from The Cancer Genome Atlas, a public database. DNA methylation gene signature consisting of five genes (SERPINA3, AP000357.4, GZMA, AC004702.2, and GREB1L) were selected. As the most accurate predictor, the area under the curve in the training and test group were 0.72 and 0.61, respectively. The signature was able to sort patients into high- and low-risk groups with meaningful overall survival rates (median: 18.36 vs 72.23 months, log-rank test, P < 0.001) in the training group, which predictive ability was validated in a test data set (median: 25.56 vs 58.80 months, log-rank test, P < 0.016). A multivariate Cox regression analysis showed the significant DNA methylation was an independent prediction prognostic factor for gastric adenocarcinoma patients. Functional analysis suggests that these signature genes may be related to pathways and biological processes associated with tumorigenesis. The significant DNA methylation gene could be a novel prediction and prognostic biomarker that both aids in the treatment and predicts the overall survival likelihoods of gastric adenocarcinoma patients.
胃腺癌是一种与死亡密切相关的癌症。为了找到与生存和预后相关的因素，从而改善康复前景，需要一个强大的特征指标。DNA甲基化在胃腺癌的发生和发展过程中起着重要作用，在此我们报告寻找一个重要的DNA甲基化基因以辅助早期诊断胃腺癌患者的研究。使用Cox比例风险回归分析和随机生存森林算法分析来自公共数据库“癌症基因组图谱”的胃腺癌患者的DNA甲基化数据。选择了由五个基因（SERPINA3、AP000357.4、GZMA、AC004702.2和GREB1L）组成的DNA甲基化基因特征指标。作为最准确的预测指标，训练组和测试组的曲线下面积分别为0.72和0.61。该特征指标能够将训练组患者分为高风险和低风险组，两组的总生存率具有显著差异（中位数：18.36个月对72.23个月，对数秩检验，P < 0.001），其预测能力在测试数据集中得到验证（中位数：25.56个月对58.80个月，对数秩检验，P < 0.016）。多变量Cox回归分析表明，显著的DNA甲基化是胃腺癌患者独立的预测预后因素。功能分析表明，这些特征基因可能与肿瘤发生相关的信号通路和生物学过程有关。这个显著的DNA甲基化基因可能是一种新型的预测和预后生物标志物，有助于胃腺癌患者的治疗并预测其总生存可能性。
