Department of Epidemiology and Statistics, School of Public Health, Hebei Key Laboratory of Environment and Human Health, Hebei Medical University, Shijiazhuang 050017, P.R. China.
Department of Medical Record, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, P.R. China.
Aging (Albany NY). 2021 Jun 28;13(12):16600-16619. doi: 10.18632/aging.203179.
Evidence suggests that abnormal DNA methylation patterns play a crucial role in the etiology and pathogenesis of colon adenocarcinoma (COAD). In this study, we identified a total of 97 methylation-driven genes (MDGs) through a comprehensive analysis of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate Cox regression analysis identified four MDGs (, , 1, and ) associated with overall survival (OS) in COAD patients. A risk prediction model was then developed based on these four MDGs to predict the prognosis of COAD patients. We also created a nomogram that incorporated risk scores, age, and TNM stage to promote a personalized prediction of OS in COAD patients. Compared with the traditional TNM staging system, our new nomogram was better at predicting the OS of COAD patients. In cell experiments, we confirmed that the mRNA expression levels of and were regulated by the methylation of their promoter regions. Moreover, immunohistochemistry showed that and were potential prognostic biomarkers for COAD patients. In summary, we have established a risk prediction model and nomogram that might be effectively utilized to promote the prediction of OS in COAD patients.
有证据表明,异常的 DNA 甲基化模式在结肠腺癌 (COAD) 的病因和发病机制中起着至关重要的作用。在这项研究中,我们通过对癌症基因组图谱 (TCGA) 和基因表达综合数据库 (GEO) 的综合分析,共鉴定出 97 个甲基化驱动基因 (MDGs)。单变量 Cox 回归分析确定了四个与 COAD 患者总生存期 (OS) 相关的 MDGs(、、1 和)。然后,基于这四个 MDGs 构建了一个风险预测模型,以预测 COAD 患者的预后。我们还创建了一个包含风险评分、年龄和 TNM 分期的列线图,以促进 COAD 患者 OS 的个性化预测。与传统的 TNM 分期系统相比,我们的新列线图更能预测 COAD 患者的 OS。在细胞实验中,我们证实了和的 mRNA 表达水平受其启动子区域甲基化的调节。此外,免疫组织化学显示和可能是 COAD 患者的潜在预后生物标志物。总之,我们建立了一个风险预测模型和列线图,可能有效地用于促进 COAD 患者 OS 的预测。