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基于加权基因共表达网络分析鉴定胰腺癌类型相关因素。

Identification of pancreatic cancer type related factors by Weighted Gene Co-Expression Network Analysis.

机构信息

Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3# Eastern Qingchun Road, Hangzhou, 310016, Zhejiang, People's Republic of China.

Department of ICU, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Xiasha Campus, 368# Xiasha Road, Hangzhou, 310019, Zhejiang, People's Republic of China.

出版信息

Med Oncol. 2020 Mar 21;37(4):33. doi: 10.1007/s12032-020-1339-0.

Abstract

This study aims to identify the core modules associated with pancreatic cancer (PC) types and the ncRNAs and transcription factors (TFs) that regulate core module genes by weighted gene co-expression network analysis (WGCNA). WGCNA was used to analyze the union of genes related to PC in NCBI and OMIM databases and the differentially expressed genes screened by TCGA-PAAD database. Samples were clustered according to gene expression in gene modules and Fisher exact method was performed. GO and KEGG were used for enrichment analysis to visually display module genes and screen driver genes. Hypergeometric test method was used to calculate pivot nodes among ncRNAs, TFs and mRNA based on RAID 2.0 and TRRUST v2 databases. The blue and yellow modules were identified as the core modules associated with PC types. MST1R, TMPRSS, MIR198, SULF1, COL1A1 and FAP were the core genes in the modules. Hypergeometric test results showed that ANCR, miR-3134, MT1DP, LOC154449, LOC28329 and other ncRNAs were key factors driving blue module genes, while LINC-ROR, UCA1, SNORD114-4, HEIH, SNORD114-6 and other ncRNAs were key factors driving yellow module genes. TFs with significant regulatory effect on blue module included LCOR, PIAS4, ZEB1, SNAI2, SMARCA4, etc. and on yellow module included HOXC6, PER2, HOXD3, TWIST2, VHL, etc. The core modules associated with PC types were proved as yellow and blue modules, and important ncRNAs and TFs regulating yellow and blue modules were found. This study provides relevant evidence for further identification of PC types.

摘要

本研究旨在通过加权基因共表达网络分析(WGCNA)鉴定与胰腺癌(PC)类型相关的核心模块以及调节核心模块基因的非编码 RNA(ncRNA)和转录因子(TF)。使用 WGCNA 分析 NCBI 和 OMIM 数据库中与 PC 相关的基因的联合以及 TCGA-PAAD 数据库中筛选的差异表达基因。根据基因模块中的基因表达对样品进行聚类,并进行 Fisher 精确检验。GO 和 KEGG 用于富集分析,以直观显示模块基因并筛选驱动基因。基于 RAID 2.0 和 TRRUST v2 数据库,使用超几何检验方法计算 ncRNA、TF 和 mRNA 之间的枢纽节点。鉴定蓝色和黄色模块为与 PC 类型相关的核心模块。MST1R、TMPRSS、MIR198、SULF1、COL1A1 和 FAP 是模块中的核心基因。超几何检验结果表明,ANCR、miR-3134、MT1DP、LOC154449、LOC28329 等 ncRNA 是驱动蓝色模块基因的关键因素,而 LINC-ROR、UCA1、SNORD114-4、HEIH、SNORD114-6 等 ncRNA 是驱动黄色模块基因的关键因素。对蓝色模块具有显著调节作用的 TF 包括 LCOR、PIAS4、ZEB1、SNAI2、SMARCA4 等,对黄色模块具有显著调节作用的 TF 包括 HOXC6、PER2、HOXD3、TWIST2、VHL 等。与 PC 类型相关的核心模块被证明为黄色和蓝色模块,发现了调节黄色和蓝色模块的重要 ncRNA 和 TF。本研究为进一步鉴定 PC 类型提供了相关证据。

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