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异常的 CpG 甲基化影响肺腺癌中预测生存的基因表达。

Aberrant CpG-methylation affects genes expression predicting survival in lung adenocarcinoma.

机构信息

Department of Respiratory Medicine, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.

Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

出版信息

Cancer Med. 2018 Nov;7(11):5716-5726. doi: 10.1002/cam4.1834. Epub 2018 Oct 23.

Abstract

Lung adenocarcinoma (LUAD) is a common diagnosed disease with high-mortality rate, and its prognostic implications are under discovered. DNA methylation aberrations are not only an important event for dysregulation of gene expression during tumorigenesis but also a revolution in epigenetics by identifying key prognostic biomarkers for multiple cancers. In this study, we analyzed methylation status of 485 578 CpG sites and RNA-seq transcriptomes of 20 532 genes for 1095 LUAD samples in TCGA database. The association between DNA methylation and the prognostic value of the corresponding gene expression was identified as well. In total, ten aberrantly methylated and dysregulated genes (AURKA, BLK, CNTN2, HMGA1, PTTG1, TNS4, DAPK2, MFSD2A, THSD1, and WNT7A) were highlighted which were significantly correlated with overall survival of 492 LUAD patients, which were all reported as tumor-associated genes in other various cancers and worthy of further investigated and might be used as therapeutic targets for LUAD. Together, methylation aberrances regulate gene expression level during tumorigenesis and influence prognosis of LUAD patients. Integrating knowledge of epigenetics and expression of genes can be useful for an in-depth understanding of cancer mechanism and for the eventual purpose of precisely prognostic and therapeutic target verification.

摘要

肺腺癌(LUAD)是一种常见的高死亡率疾病,其预后意义尚未被发现。DNA 甲基化异常不仅是肿瘤发生过程中基因表达失调的重要事件,而且通过鉴定多种癌症的关键预后生物标志物,也是表观遗传学的一场革命。在这项研究中,我们分析了 TCGA 数据库中 1095 个 LUAD 样本的 485578 个 CpG 位点的甲基化状态和 20532 个基因的 RNA-seq 转录组。还确定了 DNA 甲基化与相应基因表达的预后价值之间的关联。总的来说,有十个异常甲基化和失调的基因(AURKA、BLK、CNTN2、HMGA1、PTTG1、TNS4、DAPK2、MFSD2A、THSD1 和 WNT7A)被强调,它们与 492 名 LUAD 患者的总生存率显著相关,这些基因在其他各种癌症中均被报道为肿瘤相关基因,值得进一步研究,并且可能被用作 LUAD 的治疗靶点。总之,甲基化异常在肿瘤发生过程中调节基因表达水平,并影响 LUAD 患者的预后。整合表观遗传学和基因表达的知识对于深入了解癌症机制以及最终准确预测预后和治疗靶点验证是有用的。

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