Analysis of DNA methylation-driven genes for predicting the prognosis of patients with colorectal cancer.
Analysis of DNA methylation-driven genes for predicting the prognosis of patients with colorectal cancer.
复制标题
DNA甲基化驱动基因分析预测结直肠癌患者预后
DOI：
10.18632/aging.103949
复制
发表时间：
2020-11-16
期刊：
影响因子：
--
通讯作者：
Wei M
中科院分区：
文献类型：
--
作者：
Fu B;Du C;Wu Z;Li M;Zhao Y;Liu X;Wu H;Wei M
异常启动子甲基化和随之而来的异常基因表达是促进结直肠癌发生的重要表观遗传机制。然而，这种甲基化驱动基因在结直肠癌（CRC）中的预后意义仍然不清楚。本文通过综合分析表达谱和来自癌症基因组图谱（TCGA）数据库的匹配DNA甲基化数据，共鉴定出181个基因为CRC的甲基化驱动分子特征。其中，POU4F1、NOVA1、MAGEA1、SLCO4C1和IZUMO2这5个基因特征被开发为预测结直肠癌临床结局的风险评估模型。Kaplan-Meier分析和Harrell’s C指数显示，风险评估模型显著区分高危组和低危组患者（p值< 0.0001，log-rank检验，HR: 2.034, 95% CI: 1.419 ~ 2.916， C指数：0.655）。通过受试者工作特征（ROC）分析验证其敏感性和特异性。此外，在高危组和低危组之间观察到不同的药物治疗反应。事实上，甲基化驱动的基因标记可以作为一种独立的预后评估生物标志物，用于评估结直肠癌患者的OS并指导药物治疗。与已知的生物标志物相比，甲基化驱动的基因标记可以揭示交叉组学分子特征，从而改善临床分层和预后。
Aberrant promoter methylation and ensuing abnormal gene expression are important epigenetic mechanisms that contribute to colorectal oncogenesis. Yet, the prognostic significance of such methylation-driven genes in colorectal cancer (CRC) remains obscure. Herein, a total of 181 genes were identified as the methylation-driven molecular features of CRC by integrated analysis of the expression profiles and the matched DNA methylation data from The Cancer Genome Atlas (TCGA) database. Among them, a five-gene signature (POU4F1, NOVA1, MAGEA1, SLCO4C1, and IZUMO2) was developed as a risk assessment model for predicting the clinical outcomes in CRC. The Kaplan–Meier analysis and Harrell’s C index demonstrated that the risk assessment model significantly distinguished the patients in high or low-risk groups (p-value < 0.0001 log-rank test, HR: 2.034, 95% CI: 1.419-2.916, C index: 0.655). The sensitivity and specificity were validated by the receiver operating characteristic (ROC) analysis. Furthermore, different pharmaceutical treatment responses were observed between the high-risk and low-risk groups. Indeed, the methylation-driven gene signature could act as an independent prognostic evaluation biomarker for assessing the OS of CRC patients and guiding the pharmaceutical treatment. Compared with known biomarkers, the methylation-driven gene signature could reveal cross-omics molecular features for improving clinical stratification and prognosis.
登录
查看更多内容
影响因子：
48
作者：
Flusberg, Benjamin A.;Webster, Dale R.;Lee, Jessica H.;Travers, Kevin J.;Olivares, Eric C.;Clark, Tyson A.;Korlach, Jonas;Turner, Stephen W.
通讯作者：
Turner, Stephen W.
DOI：
10.1016/j.bbrc.2009.12.095
发表时间：
2010-01-15
影响因子：
3.1
作者：
Kosuri, K. V.;Wu, X.;Wang, L.;Villalona-Calero, M. A.;Otterson, G. A.
通讯作者：
Otterson, G. A.
影响因子：
3.4
作者：
Ge, Xiaosong;Chen, Yuanbin;Jia, Weihua
通讯作者：
Jia, Weihua
影响因子：
5.8
作者：
Lu, Tong;Chen, Di;Jiao, Wenjie
通讯作者：
Jiao, Wenjie
影响因子：
8
作者：
Sayed, Mohammed E.;Yuan, Laura;Ludlow, Andrew T.
通讯作者：
Ludlow, Andrew T.