Integrated Gene Expression Profiling Analysis Reveals Probable Molecular Mechanism and Candidate Biomarker in Anti-TNFα Non-Response IBD Patients

Integrated Gene Expression Profiling Analysis Reveals Probable Molecular Mechanism and Candidate Biomarker in Anti-TNFα Non-Response IBD Patients

Yifan Liu, Yantao Duan, Yousheng Li Department of General Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011, People’s Republic of ChinaCorrespondence: Yousheng LiDepartment of General Surgery, Shanghai Ninth People&rsq...

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Autores principales: Liu Y, Duan Y, Li Y
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2020
Materias:
differentially expressed genes
inflammatory bowel disease
toll-like receptor pathway
fcγr signaling
anti-tnfα therapy
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Acceso en línea:https://doaj.org/article/ff8d04fc739044008d572e920a36110f
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spelling oai:doaj.org-article:ff8d04fc739044008d572e920a36110f2021-12-02T08:39:39ZIntegrated Gene Expression Profiling Analysis Reveals Probable Molecular Mechanism and Candidate Biomarker in Anti-TNFα Non-Response IBD Patients1178-7031https://doaj.org/article/ff8d04fc739044008d572e920a36110f2020-02-01T00:00:00Zhttps://www.dovepress.com/integrated-gene-expression-profiling-analysis-reveals-probable-molecul-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Yifan Liu, Yantao Duan, Yousheng Li Department of General Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011, People’s Republic of ChinaCorrespondence: Yousheng LiDepartment of General Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011, People’s Republic of ChinaEmail liyousheng@shemu.edu.cnPurpose: To explore the molecular mechanism and search for candidate biomarkers in the gene expression profile of IBD patients associated with the response to anti-TNFα agents.Methods: Differentially expressed genes (DEGs) of response vs non-response IBD patients in datasets GSE12251, GSE16879, and GSE23597 were integrated using NetworkAnalyst. We conducted functional enrichment analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and extracted hub genes from the protein–protein interaction network. The proportion of immune cell types was estimated via CIBERSORT. ROC curve analysis and binomial Lasso regression were applied to assess the expression level of hub genes in datasets GSE12251, GSE16879, and GSE23597, and another two datasets GSE107865 and GSE42296.Results: A total of 287 DEGs were obtained from the integrated dataset. They were enriched in 14 Gene Ontology terms and 11 KEGG pathways. Polarization from M2 to M1 macrophages was relatively high in non-response individuals. We found nine hub genes (TLR4, TLR1, TLR8, CCR1, CD86, CCL4, HCK, and FCGR2A), mainly related to the interaction between Toll-like Receptor (TLR) pathway and FcγR signaling in non-response anti-TNFα individuals. FCGR2A, HCK, TLR1, TLR4, TLR8, and CCL4 show great value for prediction in intestinal tissue. Besides, FCGR2A, HCK, and TLR8 might be candidate blood biomarkers of anti-TNFα non-response IBD patients.Conclusion: Over-activated interaction between FcγR-TLR axis in the innate immune cells of IBD patients might be used to identify non-response individuals and increased our understanding of resistance to anti-TNFα therapy.Keywords: differentially expressed genes, inflammatory bowel disease, toll-like receptor pathway, FcγR signaling, anti-TNFα therapyLiu YDuan YLi YDove Medical Pressarticledifferentially expressed genesinflammatory bowel diseasetoll-like receptor pathwayfcγr signalinganti-tnfα therapyPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 13, Pp 81-95 (2020)
institution DOAJ
collection DOAJ
language EN
topic differentially expressed genes
inflammatory bowel disease
toll-like receptor pathway
fcγr signaling
anti-tnfα therapy
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
spellingShingle differentially expressed genes
inflammatory bowel disease
toll-like receptor pathway
fcγr signaling
anti-tnfα therapy
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Liu Y
Duan Y
Li Y
Integrated Gene Expression Profiling Analysis Reveals Probable Molecular Mechanism and Candidate Biomarker in Anti-TNFα Non-Response IBD Patients
description Yifan Liu, Yantao Duan, Yousheng Li Department of General Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011, People’s Republic of ChinaCorrespondence: Yousheng LiDepartment of General Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011, People’s Republic of ChinaEmail liyousheng@shemu.edu.cnPurpose: To explore the molecular mechanism and search for candidate biomarkers in the gene expression profile of IBD patients associated with the response to anti-TNFα agents.Methods: Differentially expressed genes (DEGs) of response vs non-response IBD patients in datasets GSE12251, GSE16879, and GSE23597 were integrated using NetworkAnalyst. We conducted functional enrichment analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and extracted hub genes from the protein–protein interaction network. The proportion of immune cell types was estimated via CIBERSORT. ROC curve analysis and binomial Lasso regression were applied to assess the expression level of hub genes in datasets GSE12251, GSE16879, and GSE23597, and another two datasets GSE107865 and GSE42296.Results: A total of 287 DEGs were obtained from the integrated dataset. They were enriched in 14 Gene Ontology terms and 11 KEGG pathways. Polarization from M2 to M1 macrophages was relatively high in non-response individuals. We found nine hub genes (TLR4, TLR1, TLR8, CCR1, CD86, CCL4, HCK, and FCGR2A), mainly related to the interaction between Toll-like Receptor (TLR) pathway and FcγR signaling in non-response anti-TNFα individuals. FCGR2A, HCK, TLR1, TLR4, TLR8, and CCL4 show great value for prediction in intestinal tissue. Besides, FCGR2A, HCK, and TLR8 might be candidate blood biomarkers of anti-TNFα non-response IBD patients.Conclusion: Over-activated interaction between FcγR-TLR axis in the innate immune cells of IBD patients might be used to identify non-response individuals and increased our understanding of resistance to anti-TNFα therapy.Keywords: differentially expressed genes, inflammatory bowel disease, toll-like receptor pathway, FcγR signaling, anti-TNFα therapy
format article
author Liu Y
Duan Y
Li Y
author_facet Liu Y
Duan Y
Li Y
author_sort Liu Y
title Integrated Gene Expression Profiling Analysis Reveals Probable Molecular Mechanism and Candidate Biomarker in Anti-TNFα Non-Response IBD Patients
title_short Integrated Gene Expression Profiling Analysis Reveals Probable Molecular Mechanism and Candidate Biomarker in Anti-TNFα Non-Response IBD Patients
title_full Integrated Gene Expression Profiling Analysis Reveals Probable Molecular Mechanism and Candidate Biomarker in Anti-TNFα Non-Response IBD Patients
title_fullStr Integrated Gene Expression Profiling Analysis Reveals Probable Molecular Mechanism and Candidate Biomarker in Anti-TNFα Non-Response IBD Patients
title_full_unstemmed Integrated Gene Expression Profiling Analysis Reveals Probable Molecular Mechanism and Candidate Biomarker in Anti-TNFα Non-Response IBD Patients
title_sort integrated gene expression profiling analysis reveals probable molecular mechanism and candidate biomarker in anti-tnfα non-response ibd patients
publisher Dove Medical Press
publishDate 2020
url https://doaj.org/article/ff8d04fc739044008d572e920a36110f
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AT duany integratedgeneexpressionprofilinganalysisrevealsprobablemolecularmechanismandcandidatebiomarkerinantitnfalphanonresponseibdpatients
AT liy integratedgeneexpressionprofilinganalysisrevealsprobablemolecularmechanismandcandidatebiomarkerinantitnfalphanonresponseibdpatients
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