Identification of Unique Transcriptomic Signatures and Hub Genes Through RNA Sequencing and Integrated WGCNA and PPI Network Analysis in Nonerosive Reflux Disease

Ye Zhao,1,&ast; Teng Ma,2,&ast; Duowu Zou1 1Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Repub...

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Autores principales:	Zhao Y, Ma T, Zou D
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	nonerosive reflux disease rna sequencing hub gene bioinformatics analysis wgcna validation Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/01adb9e065d64429930fe81a5dedbaa3
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spelling	oai:doaj.org-article:01adb9e065d64429930fe81a5dedbaa32021-11-23T18:43:01ZIdentification of Unique Transcriptomic Signatures and Hub Genes Through RNA Sequencing and Integrated WGCNA and PPI Network Analysis in Nonerosive Reflux Disease1178-7031https://doaj.org/article/01adb9e065d64429930fe81a5dedbaa32021-11-01T00:00:00Zhttps://www.dovepress.com/identification-of-unique-transcriptomic-signatures-and-hub-genes-throu-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Ye Zhao,1,&ast; Teng Ma,2,&ast; Duowu Zou1 1Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Duowu Zou 200025 Tel +86-2164370045-665444Email zdwrjxh66@sjtu.edu.cnPurpose: Transcriptomic studies on gastroesophageal reflux disease are scarce, and gene expression signatures in nonerosive reflux disease (NERD) remain elusive. The aim of the study was to identify gene expression profiles and potential hub genes in NERD.Patients and Methods: We performed RNA sequencing on biopsy samples from nine consecutive patients with NERD and six healthy controls. Differentially expressed genes (DEGs) were analysed with the DESeq2 R package. A DEG-based protein–protein interaction (PPI) network was constructed to filter hub genes using Cytoscape. Weighted gene coexpression network analysis (WGCNA) was conducted to identify the coexpression relationships of all modules and explore the relationship between gene sets and clinical traits.Results: In total, 1195 DEGs were identified, including 649 upregulated and 546 downregulated genes involved in regulating the inflammatory response and epithelial cell differentiation. Overlap of the PPI and WGCNA networks identified five shared genes, namely, THY1, BMP2, LOX, KDR and MMP9, as candidate hub genes in NERD. Quantitative PCR analysis of the expression of these five genes confirmed the sequencing results. Receiver operating characteristic analyses indicated that these hub genes had diagnostic potential for NERD patients. Gene set enrichment analysis confirmed that each hub gene was closely associated with the pathophysiological processes of NERD. In addition, a regulatory network comprising 42 transcription factors (TFs), 28 miRNAs and 5 hub genes was established.Conclusion: The five core genes may be promising biomarkers of NERD. The TF/miRNA/hub gene network can improve the understanding of the molecular mechanisms underlying disease progression.Keywords: nonerosive reflux disease, RNA sequencing, hub gene, bioinformatics analysis, WGCNA, validationZhao YMa TZou DDove Medical Pressarticlenonerosive reflux diseaserna sequencinghub genebioinformatics analysiswgcnavalidationPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 6143-6156 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nonerosive reflux disease rna sequencing hub gene bioinformatics analysis wgcna validation Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	nonerosive reflux disease rna sequencing hub gene bioinformatics analysis wgcna validation Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Zhao Y Ma T Zou D Identification of Unique Transcriptomic Signatures and Hub Genes Through RNA Sequencing and Integrated WGCNA and PPI Network Analysis in Nonerosive Reflux Disease
description	Ye Zhao,1,&ast; Teng Ma,2,&ast; Duowu Zou1 1Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Duowu Zou 200025 Tel +86-2164370045-665444Email zdwrjxh66@sjtu.edu.cnPurpose: Transcriptomic studies on gastroesophageal reflux disease are scarce, and gene expression signatures in nonerosive reflux disease (NERD) remain elusive. The aim of the study was to identify gene expression profiles and potential hub genes in NERD.Patients and Methods: We performed RNA sequencing on biopsy samples from nine consecutive patients with NERD and six healthy controls. Differentially expressed genes (DEGs) were analysed with the DESeq2 R package. A DEG-based protein–protein interaction (PPI) network was constructed to filter hub genes using Cytoscape. Weighted gene coexpression network analysis (WGCNA) was conducted to identify the coexpression relationships of all modules and explore the relationship between gene sets and clinical traits.Results: In total, 1195 DEGs were identified, including 649 upregulated and 546 downregulated genes involved in regulating the inflammatory response and epithelial cell differentiation. Overlap of the PPI and WGCNA networks identified five shared genes, namely, THY1, BMP2, LOX, KDR and MMP9, as candidate hub genes in NERD. Quantitative PCR analysis of the expression of these five genes confirmed the sequencing results. Receiver operating characteristic analyses indicated that these hub genes had diagnostic potential for NERD patients. Gene set enrichment analysis confirmed that each hub gene was closely associated with the pathophysiological processes of NERD. In addition, a regulatory network comprising 42 transcription factors (TFs), 28 miRNAs and 5 hub genes was established.Conclusion: The five core genes may be promising biomarkers of NERD. The TF/miRNA/hub gene network can improve the understanding of the molecular mechanisms underlying disease progression.Keywords: nonerosive reflux disease, RNA sequencing, hub gene, bioinformatics analysis, WGCNA, validation
format	article
author	Zhao Y Ma T Zou D
author_facet	Zhao Y Ma T Zou D
author_sort	Zhao Y
title	Identification of Unique Transcriptomic Signatures and Hub Genes Through RNA Sequencing and Integrated WGCNA and PPI Network Analysis in Nonerosive Reflux Disease
title_short	Identification of Unique Transcriptomic Signatures and Hub Genes Through RNA Sequencing and Integrated WGCNA and PPI Network Analysis in Nonerosive Reflux Disease
title_full	Identification of Unique Transcriptomic Signatures and Hub Genes Through RNA Sequencing and Integrated WGCNA and PPI Network Analysis in Nonerosive Reflux Disease
title_fullStr	Identification of Unique Transcriptomic Signatures and Hub Genes Through RNA Sequencing and Integrated WGCNA and PPI Network Analysis in Nonerosive Reflux Disease
title_full_unstemmed	Identification of Unique Transcriptomic Signatures and Hub Genes Through RNA Sequencing and Integrated WGCNA and PPI Network Analysis in Nonerosive Reflux Disease
title_sort	identification of unique transcriptomic signatures and hub genes through rna sequencing and integrated wgcna and ppi network analysis in nonerosive reflux disease
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/01adb9e065d64429930fe81a5dedbaa3
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_version_	1718416132571922432

Identification of Unique Transcriptomic Signatures and Hub Genes Through RNA Sequencing and Integrated WGCNA and PPI Network Analysis in Nonerosive Reflux Disease

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