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肾母细胞瘤中关键致癌基因的鉴定。

Identification of key carcinogenic genes in Wilms' tumor.

作者信息

He Shaohua, Yang Liu, Xiao Zhixiang, Tang Kunbin, Xu Di

机构信息

Department of Pediatric Surgery, Fujian Provincial Hospital.

Unimed Scientific Inc.

出版信息

Genes Genet Syst. 2021 Oct 9;96(3):141-149. doi: 10.1266/ggs.21-00015. Epub 2021 Aug 1.

Abstract

This study aimed to probe carcinogenic genes and pathways associated with Wilms' tumor (WT) onset and malignancy progression. After screening, three datasets acquired from the Gene Expression Omnibus database were analyzed. Differentially expressed genes (DEGs) were identified and GO functional enrichment, KEGG pathway enrichment and protein-protein interaction (PPI) were analyzed. The DEGs with top fold change values or top protein interaction scores were used to analyze overall survival based on the TARGET WT dataset. Together, 866 up-regulated genes in GDS1791, 585 up-regulated genes in GDS2010, and 277 down-regulated genes in GDS4802 were found, from which 46 key DEGs were selected for further analysis. In the PPI network, hub positions included COL5A1, COL4A1, ARPP21, SPARCL1, CD86, LY96 and PPP1R12B. The top DEGs (ARPP21, SYNPO, PRRC2B, PPP1R12B, EFCAB2 and LY96) were selected for survival analysis, and they consistently showed a significantly positive correlation with poor survival. Together, five key carcinogenic genes (SYNPO, PRRC2B, PPP1R12B, EFCAB2 and LY96) were highly associated with WT onset and patient survival. These risk genes, interaction networks and enrichments should improve our understanding of the complex molecular mechanisms in WT development and help clinical applications.

摘要

本研究旨在探究与肾母细胞瘤(WT)发病及恶性进展相关的致癌基因和通路。筛选后,对从基因表达综合数据库获取的三个数据集进行了分析。鉴定了差异表达基因(DEGs),并分析了基因本体(GO)功能富集、京都基因与基因组百科全书(KEGG)通路富集及蛋白质-蛋白质相互作用(PPI)。基于TARGET WT数据集,使用具有最高倍数变化值或最高蛋白质相互作用得分的DEGs来分析总生存期。共发现GDS1791中有866个上调基因、GDS2010中有585个上调基因以及GDS4802中有277个下调基因,从中选择了46个关键DEGs进行进一步分析。在PPI网络中,中心位置包括COL5A1、COL4A1、ARPP21、SPARCL1、CD86、LY96和PPP1R12B。选择顶级DEGs(ARPP21、SYNPO、PRRC2B、PPP1R12B、EFCAB2和LY96)进行生存分析,它们均与较差的生存率呈显著正相关。共有五个关键致癌基因(SYNPO、PRRC2B、PPP1R12B、EFCAB2和LY96)与WT发病及患者生存高度相关。这些风险基因、相互作用网络和富集分析应能增进我们对WT发生复杂分子机制的理解,并有助于临床应用。

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