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鉴定一种新型与细胞周期相关的基因特征,可预测胃癌患者的生存情况。

Identification of a novel cell cycle-related gene signature predicting survival in patients with gastric cancer.

机构信息

Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.

Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China.

出版信息

J Cell Physiol. 2019 May;234(5):6350-6360. doi: 10.1002/jcp.27365. Epub 2018 Sep 21.

Abstract

Gastric cancer (GC) is one of the most fatal cancers in the world. Thousands of biomarkers have been explored that might be related to survival and prognosis via database mining. However, the prediction effect of single gene biomarkers is not specific enough. Increasing evidence suggests that gene signatures are emerging as a possible better alternative. We aimed to develop a novel gene signature to improve the prognosis prediction of GC. Using the messenger RNA (mRNA)-mining approach, we performed mRNA expression profiling in a large GC cohort (n = 375) from The Cancer Genome Atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA) was performed, and we recovered genes related to the G2/M checkpoint, which we identified with a Cox proportional regression model. We identified a set of five genes (MARCKS, CCNF, MAPK14, INCENP, and CHAF1A), which were significantly associated with overall survival (OS) in the test series. Based on this five-gene signature, the test series patients could be classified into high-risk or low-risk subgroups. Multivariate Cox regression analysis indicated that the prognostic power of this five-gene signature was independent of clinical features. In conclusion, we developed a five-gene signature related to the cell cycle that can predict survival for GC. Our findings provide novel insight that is useful for understanding cell cycle mechanisms and for identifying patients with GC with poor prognoses.

摘要

胃癌(GC)是世界上最致命的癌症之一。通过数据库挖掘,已经探索了数千种可能与生存和预后相关的生物标志物。然而,单个基因生物标志物的预测效果不够特异。越来越多的证据表明,基因特征正在成为一种可能更好的选择。我们旨在开发一种新的基因特征,以提高 GC 的预后预测。我们使用信使 RNA(mRNA)挖掘方法,对来自癌症基因组图谱(TCGA)数据库的大型 GC 队列(n=375)进行了 mRNA 表达谱分析。进行了基因集富集分析(GSEA),我们恢复了与 G2/M 检查点相关的基因,并用 Cox 比例回归模型对其进行了鉴定。我们确定了一组五个基因(MARCKS、CCNF、MAPK14、INCENP 和 CHAF1A),它们与测试系列中的总生存期(OS)显著相关。基于这个五个基因的特征,测试系列的患者可以被分为高风险或低风险亚组。多变量 Cox 回归分析表明,这个五个基因特征的预后能力独立于临床特征。总之,我们开发了一个与细胞周期相关的五个基因特征,可以预测 GC 的生存情况。我们的研究结果提供了新的见解,有助于理解细胞周期机制,并识别预后不良的 GC 患者。

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