Identification and Validation of Key Genes of Differential Correlations in Gastric Cancer

Background: Gastric cancer (GC) is aggressive cancer with a poor prognosis. Previously bulk transcriptome analysis was utilized to identify key genes correlated with the development, progression and prognosis of GC. However, due to the complexity of the genetic mutations, there is still an urgent ne...

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Main Authors: Tingna Chen, Qiuming He, Zhenxian Xiang, Rongzhang Dou, Bin Xiong
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2021.801687/full
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author Tingna Chen
Tingna Chen
Tingna Chen
Qiuming He
Qiuming He
Qiuming He
Zhenxian Xiang
Zhenxian Xiang
Zhenxian Xiang
Rongzhang Dou
Rongzhang Dou
Rongzhang Dou
Bin Xiong
Bin Xiong
Bin Xiong
author_facet Tingna Chen
Tingna Chen
Tingna Chen
Qiuming He
Qiuming He
Qiuming He
Zhenxian Xiang
Zhenxian Xiang
Zhenxian Xiang
Rongzhang Dou
Rongzhang Dou
Rongzhang Dou
Bin Xiong
Bin Xiong
Bin Xiong
author_sort Tingna Chen
collection DOAJ
description Background: Gastric cancer (GC) is aggressive cancer with a poor prognosis. Previously bulk transcriptome analysis was utilized to identify key genes correlated with the development, progression and prognosis of GC. However, due to the complexity of the genetic mutations, there is still an urgent need to recognize core genes in the regulatory network of GC.Methods: Gene expression profiles (GSE66229) were retrieved from the GEO database. Weighted correlation network analysis (WGCNA) was employed to identify gene modules mostly correlated with GC carcinogenesis. R package ‘DiffCorr’ was applied to identify differentially correlated gene pairs in tumor and normal tissues. Cytoscape was adopted to construct and visualize the gene regulatory network.Results: A total of 15 modules were detected in WGCNA analysis, among which three modules were significantly correlated with GC. Then genes in these modules were analyzed separately by “DiffCorr”. Multiple differentially correlated gene pairs were recognized and the network was visualized by the software Cytoscape. Moreover, GEMIN5 and PFDN2, which were rarely discussed in GC, were identified as key genes in the regulatory network and the differential expression was validated by real-time qPCR, WB and IHC in cell lines and GC patient tissues.Conclusions: Our research has shed light on the carcinogenesis mechanism by revealing differentially correlated gene pairs during transition from normal to tumor. We believe the application of this network-based algorithm holds great potential in inferring relationships and detecting candidate biomarkers.
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spelling doaj.art-247e63ec7be541c49b13878461277d292022-12-22T04:12:41ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-01-01910.3389/fcell.2021.801687801687Identification and Validation of Key Genes of Differential Correlations in Gastric CancerTingna Chen0Tingna Chen1Tingna Chen2Qiuming He3Qiuming He4Qiuming He5Zhenxian Xiang6Zhenxian Xiang7Zhenxian Xiang8Rongzhang Dou9Rongzhang Dou10Rongzhang Dou11Bin Xiong12Bin Xiong13Bin Xiong14Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaBackground: Gastric cancer (GC) is aggressive cancer with a poor prognosis. Previously bulk transcriptome analysis was utilized to identify key genes correlated with the development, progression and prognosis of GC. However, due to the complexity of the genetic mutations, there is still an urgent need to recognize core genes in the regulatory network of GC.Methods: Gene expression profiles (GSE66229) were retrieved from the GEO database. Weighted correlation network analysis (WGCNA) was employed to identify gene modules mostly correlated with GC carcinogenesis. R package ‘DiffCorr’ was applied to identify differentially correlated gene pairs in tumor and normal tissues. Cytoscape was adopted to construct and visualize the gene regulatory network.Results: A total of 15 modules were detected in WGCNA analysis, among which three modules were significantly correlated with GC. Then genes in these modules were analyzed separately by “DiffCorr”. Multiple differentially correlated gene pairs were recognized and the network was visualized by the software Cytoscape. Moreover, GEMIN5 and PFDN2, which were rarely discussed in GC, were identified as key genes in the regulatory network and the differential expression was validated by real-time qPCR, WB and IHC in cell lines and GC patient tissues.Conclusions: Our research has shed light on the carcinogenesis mechanism by revealing differentially correlated gene pairs during transition from normal to tumor. We believe the application of this network-based algorithm holds great potential in inferring relationships and detecting candidate biomarkers.https://www.frontiersin.org/articles/10.3389/fcell.2021.801687/fullgastric cancerdifferential correlationswitching mechanismWGCNAgene network
spellingShingle Tingna Chen
Tingna Chen
Tingna Chen
Qiuming He
Qiuming He
Qiuming He
Zhenxian Xiang
Zhenxian Xiang
Zhenxian Xiang
Rongzhang Dou
Rongzhang Dou
Rongzhang Dou
Bin Xiong
Bin Xiong
Bin Xiong
Identification and Validation of Key Genes of Differential Correlations in Gastric Cancer
Frontiers in Cell and Developmental Biology
gastric cancer
differential correlation
switching mechanism
WGCNA
gene network
title Identification and Validation of Key Genes of Differential Correlations in Gastric Cancer
title_full Identification and Validation of Key Genes of Differential Correlations in Gastric Cancer
title_fullStr Identification and Validation of Key Genes of Differential Correlations in Gastric Cancer
title_full_unstemmed Identification and Validation of Key Genes of Differential Correlations in Gastric Cancer
title_short Identification and Validation of Key Genes of Differential Correlations in Gastric Cancer
title_sort identification and validation of key genes of differential correlations in gastric cancer
topic gastric cancer
differential correlation
switching mechanism
WGCNA
gene network
url https://www.frontiersin.org/articles/10.3389/fcell.2021.801687/full
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