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Identification of Inflammation-Related Biomarkers in Diabetes of the Exocrine Pancreas With the Use of Weighted Gene Co-Expression Network Analysis

Diabetes of the exocrine pancreas (DEP), also commonly described as pancreatogenic diabetes mellitus, is a type of diabetes secondary to abnormalities in pancreatic or exocrine secretion of the pancreas. However, its pathogenesis is not yet known. The aim of this article was to explore the biomarker...

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Autores principales: Li, Guoqing, Sun, Jinfang, Zhang, Jun, Lv, Yingqi, Liu, Dechen, Zhu, Xiangyun, Qi, Liang, Chen, Zhiwei, Ye, Zheng, Su, Xianghui, Li, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046596/
https://www.ncbi.nlm.nih.gov/pubmed/35498402
http://dx.doi.org/10.3389/fendo.2022.839865
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author Li, Guoqing
Sun, Jinfang
Zhang, Jun
Lv, Yingqi
Liu, Dechen
Zhu, Xiangyun
Qi, Liang
Chen, Zhiwei
Ye, Zheng
Su, Xianghui
Li, Ling
author_facet Li, Guoqing
Sun, Jinfang
Zhang, Jun
Lv, Yingqi
Liu, Dechen
Zhu, Xiangyun
Qi, Liang
Chen, Zhiwei
Ye, Zheng
Su, Xianghui
Li, Ling
author_sort Li, Guoqing
collection PubMed
description Diabetes of the exocrine pancreas (DEP), also commonly described as pancreatogenic diabetes mellitus, is a type of diabetes secondary to abnormalities in pancreatic or exocrine secretion of the pancreas. However, its pathogenesis is not yet known. The aim of this article was to explore the biomarkers of DEP and their potential molecular mechanisms. Based on GSE76896 dataset, which was acquired from Gene Expression Omnibus (GEO), we identified 373 genes by weighted gene co-expression network analysis (WGCNA) and differential expression analysis. In addition, protein–protein interaction (PPI) network analysis and cytoHubba were used to screen potential hub genes. Five hub genes were determined, comprising Toll-like receptor 4 (TLR4), ITGAM, ITGB2, PTPRC, and CSF1R. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways suggested macrophage activation and Toll-like receptor signaling pathway as important pathophysiological features of DEP. CIBERSORT suggested that TLR4 may regulate the immune pathway via macrophages. Next, we validated the expression and receiver operating characteristic curve (ROC) of the hub genes using the GSE164416 dataset. In addition, we used miRNet to predict the target miRNAs of hub genes and intersected them with common miRNAs in diabetes from the Human MicroRNA Disease Database (HMDD), which was used to propose a possible mechanistic model for DEP. The miRNA–mRNA network showed that has-miR-155-5p/has-miR-27a-3p/has-miR-21-5p-TLR4 might lead to TLR4 signaling pathway activation in DEP. In conclusion, we identified five hub genes, namely, TLR4, ITGAM, ITGB2, PTPRC, and CSF1R, as biomarkers to aid in the diagnosis of DEP and conducted an in-depth study of the pathogenesis of DEP at the genetic level.
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spelling pubmed-90465962022-04-29 Identification of Inflammation-Related Biomarkers in Diabetes of the Exocrine Pancreas With the Use of Weighted Gene Co-Expression Network Analysis Li, Guoqing Sun, Jinfang Zhang, Jun Lv, Yingqi Liu, Dechen Zhu, Xiangyun Qi, Liang Chen, Zhiwei Ye, Zheng Su, Xianghui Li, Ling Front Endocrinol (Lausanne) Endocrinology Diabetes of the exocrine pancreas (DEP), also commonly described as pancreatogenic diabetes mellitus, is a type of diabetes secondary to abnormalities in pancreatic or exocrine secretion of the pancreas. However, its pathogenesis is not yet known. The aim of this article was to explore the biomarkers of DEP and their potential molecular mechanisms. Based on GSE76896 dataset, which was acquired from Gene Expression Omnibus (GEO), we identified 373 genes by weighted gene co-expression network analysis (WGCNA) and differential expression analysis. In addition, protein–protein interaction (PPI) network analysis and cytoHubba were used to screen potential hub genes. Five hub genes were determined, comprising Toll-like receptor 4 (TLR4), ITGAM, ITGB2, PTPRC, and CSF1R. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways suggested macrophage activation and Toll-like receptor signaling pathway as important pathophysiological features of DEP. CIBERSORT suggested that TLR4 may regulate the immune pathway via macrophages. Next, we validated the expression and receiver operating characteristic curve (ROC) of the hub genes using the GSE164416 dataset. In addition, we used miRNet to predict the target miRNAs of hub genes and intersected them with common miRNAs in diabetes from the Human MicroRNA Disease Database (HMDD), which was used to propose a possible mechanistic model for DEP. The miRNA–mRNA network showed that has-miR-155-5p/has-miR-27a-3p/has-miR-21-5p-TLR4 might lead to TLR4 signaling pathway activation in DEP. In conclusion, we identified five hub genes, namely, TLR4, ITGAM, ITGB2, PTPRC, and CSF1R, as biomarkers to aid in the diagnosis of DEP and conducted an in-depth study of the pathogenesis of DEP at the genetic level. Frontiers Media S.A. 2022-04-14 /pmc/articles/PMC9046596/ /pubmed/35498402 http://dx.doi.org/10.3389/fendo.2022.839865 Text en Copyright © 2022 Li, Sun, Zhang, Lv, Liu, Zhu, Qi, Chen, Ye, Su and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Li, Guoqing
Sun, Jinfang
Zhang, Jun
Lv, Yingqi
Liu, Dechen
Zhu, Xiangyun
Qi, Liang
Chen, Zhiwei
Ye, Zheng
Su, Xianghui
Li, Ling
Identification of Inflammation-Related Biomarkers in Diabetes of the Exocrine Pancreas With the Use of Weighted Gene Co-Expression Network Analysis
title Identification of Inflammation-Related Biomarkers in Diabetes of the Exocrine Pancreas With the Use of Weighted Gene Co-Expression Network Analysis
title_full Identification of Inflammation-Related Biomarkers in Diabetes of the Exocrine Pancreas With the Use of Weighted Gene Co-Expression Network Analysis
title_fullStr Identification of Inflammation-Related Biomarkers in Diabetes of the Exocrine Pancreas With the Use of Weighted Gene Co-Expression Network Analysis
title_full_unstemmed Identification of Inflammation-Related Biomarkers in Diabetes of the Exocrine Pancreas With the Use of Weighted Gene Co-Expression Network Analysis
title_short Identification of Inflammation-Related Biomarkers in Diabetes of the Exocrine Pancreas With the Use of Weighted Gene Co-Expression Network Analysis
title_sort identification of inflammation-related biomarkers in diabetes of the exocrine pancreas with the use of weighted gene co-expression network analysis
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046596/
https://www.ncbi.nlm.nih.gov/pubmed/35498402
http://dx.doi.org/10.3389/fendo.2022.839865
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