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Identification of the Shared Gene Signatures and Biological Mechanism in Type 2 Diabetes and Pancreatic Cancer

BACKGROUND: The relationship between pancreatic cancer (PC) and type 2 diabetes mellitus (T2DM) has long been widely recognized, but the interaction mechanisms are still unknown. This study was aimed to investigate the shared gene signatures and molecular processes between PC and T2DM. METHODS: The...

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Autores principales: Hu, Yifang, Zeng, Ni, Ge, Yaoqi, Wang, Dan, Qin, Xiaoxuan, Zhang, Wensong, Jiang, Feng, Liu, Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010232/
https://www.ncbi.nlm.nih.gov/pubmed/35432196
http://dx.doi.org/10.3389/fendo.2022.847760
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author Hu, Yifang
Zeng, Ni
Ge, Yaoqi
Wang, Dan
Qin, Xiaoxuan
Zhang, Wensong
Jiang, Feng
Liu, Yun
author_facet Hu, Yifang
Zeng, Ni
Ge, Yaoqi
Wang, Dan
Qin, Xiaoxuan
Zhang, Wensong
Jiang, Feng
Liu, Yun
author_sort Hu, Yifang
collection PubMed
description BACKGROUND: The relationship between pancreatic cancer (PC) and type 2 diabetes mellitus (T2DM) has long been widely recognized, but the interaction mechanisms are still unknown. This study was aimed to investigate the shared gene signatures and molecular processes between PC and T2DM. METHODS: The Gene Expression Omnibus (GEO) database was used to retrieve the RNA sequence and patient information of PC and T2DM. Weighted gene co-expression network analysis (WGCNA) was performed to discover a co-expression network associated with PC and T2DM. Enrichment analysis of shared genes present in PC and T2DM was performed by ClueGO software. These results were validated in the other four cohorts based on differential gene analysis. The predictive significance of S100A6 in PC was evaluated using univariate and multivariate Cox analyses, as well as Kaplan–Meier plots. The biological process of S100A6 enrichment in PC was detected using Gene Set Enrichment Analysis (GSEA). The involvement of S100A6 in the tumor immune microenvironment (TIME) was assessed by CIBERSORT. In vitro assays were used to further confirm the function of S100A6 in PC. RESULTS: WGCNA recognized three major modules for T2DM and two major modules for PC. There were 44 shared genes identified for PC and T2DM, and Gene Ontology (GO) analysis showed that regulation of endodermal cell fate specification was primarily enriched. In addition, a key shared gene S100A6 was derived in the validation tests. S100A6 was shown to be highly expressed in PC compared to non-tumor tissues. PC patients with high S100A6 expression had worse overall survival (OS) than those with low expression. GSEA revealed that S100A6 is involved in cancer-related pathways and glycometabolism-related pathways. There is a strong relationship between S100A6 and TIME. In vitro functional assays showed that S100A6 helped to induce the PC cells’ proliferation and migration. We also proposed a diagram of common mechanisms of PC and T2DM. CONCLUSIONS: This study firstly revealed that the regulation of endodermal cell fate specification may be common pathogenesis of PC and T2DM and identified S100A6 as a possible biomarker and therapeutic target for PC and T2DM patients.
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spelling pubmed-90102322022-04-16 Identification of the Shared Gene Signatures and Biological Mechanism in Type 2 Diabetes and Pancreatic Cancer Hu, Yifang Zeng, Ni Ge, Yaoqi Wang, Dan Qin, Xiaoxuan Zhang, Wensong Jiang, Feng Liu, Yun Front Endocrinol (Lausanne) Endocrinology BACKGROUND: The relationship between pancreatic cancer (PC) and type 2 diabetes mellitus (T2DM) has long been widely recognized, but the interaction mechanisms are still unknown. This study was aimed to investigate the shared gene signatures and molecular processes between PC and T2DM. METHODS: The Gene Expression Omnibus (GEO) database was used to retrieve the RNA sequence and patient information of PC and T2DM. Weighted gene co-expression network analysis (WGCNA) was performed to discover a co-expression network associated with PC and T2DM. Enrichment analysis of shared genes present in PC and T2DM was performed by ClueGO software. These results were validated in the other four cohorts based on differential gene analysis. The predictive significance of S100A6 in PC was evaluated using univariate and multivariate Cox analyses, as well as Kaplan–Meier plots. The biological process of S100A6 enrichment in PC was detected using Gene Set Enrichment Analysis (GSEA). The involvement of S100A6 in the tumor immune microenvironment (TIME) was assessed by CIBERSORT. In vitro assays were used to further confirm the function of S100A6 in PC. RESULTS: WGCNA recognized three major modules for T2DM and two major modules for PC. There were 44 shared genes identified for PC and T2DM, and Gene Ontology (GO) analysis showed that regulation of endodermal cell fate specification was primarily enriched. In addition, a key shared gene S100A6 was derived in the validation tests. S100A6 was shown to be highly expressed in PC compared to non-tumor tissues. PC patients with high S100A6 expression had worse overall survival (OS) than those with low expression. GSEA revealed that S100A6 is involved in cancer-related pathways and glycometabolism-related pathways. There is a strong relationship between S100A6 and TIME. In vitro functional assays showed that S100A6 helped to induce the PC cells’ proliferation and migration. We also proposed a diagram of common mechanisms of PC and T2DM. CONCLUSIONS: This study firstly revealed that the regulation of endodermal cell fate specification may be common pathogenesis of PC and T2DM and identified S100A6 as a possible biomarker and therapeutic target for PC and T2DM patients. Frontiers Media S.A. 2022-03-31 /pmc/articles/PMC9010232/ /pubmed/35432196 http://dx.doi.org/10.3389/fendo.2022.847760 Text en Copyright © 2022 Hu, Zeng, Ge, Wang, Qin, Zhang, Jiang and Liu 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
Hu, Yifang
Zeng, Ni
Ge, Yaoqi
Wang, Dan
Qin, Xiaoxuan
Zhang, Wensong
Jiang, Feng
Liu, Yun
Identification of the Shared Gene Signatures and Biological Mechanism in Type 2 Diabetes and Pancreatic Cancer
title Identification of the Shared Gene Signatures and Biological Mechanism in Type 2 Diabetes and Pancreatic Cancer
title_full Identification of the Shared Gene Signatures and Biological Mechanism in Type 2 Diabetes and Pancreatic Cancer
title_fullStr Identification of the Shared Gene Signatures and Biological Mechanism in Type 2 Diabetes and Pancreatic Cancer
title_full_unstemmed Identification of the Shared Gene Signatures and Biological Mechanism in Type 2 Diabetes and Pancreatic Cancer
title_short Identification of the Shared Gene Signatures and Biological Mechanism in Type 2 Diabetes and Pancreatic Cancer
title_sort identification of the shared gene signatures and biological mechanism in type 2 diabetes and pancreatic cancer
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010232/
https://www.ncbi.nlm.nih.gov/pubmed/35432196
http://dx.doi.org/10.3389/fendo.2022.847760
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