Bioinformatics analysis identified MMP14 and COL12A1 as immune-related biomarkers associated with pancreatic adenocarcinoma prognosis

Background: Pancreatic adenocarcinoma (PAAD) is one of the most common malignant tumors with high mortality rates and a poor prognosis. There is an urgent need to determine the molecular mechanism of PAAD tumorigenesis and identify promising biomarkers for the diagnosis and targeted therapy of the...

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Autores principales:	Yuexian Li, Zhou Su, Biwei Wei, Mengbin Qin, Zhihai Liang
Formato:	article
Lenguaje:	EN
Publicado:	AIMS Press 2021
Materias:	pancreatic adenocarcinoma mmp14 col12a1 prognosis biomarker bioinformatics analysis Biotechnology TP248.13-248.65 Mathematics QA1-939
Acceso en línea:	https://doaj.org/article/0d29a33c30ea4b558df607fdd3321776
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spelling	oai:doaj.org-article:0d29a33c30ea4b558df607fdd33217762021-11-09T05:53:41ZBioinformatics analysis identified MMP14 and COL12A1 as immune-related biomarkers associated with pancreatic adenocarcinoma prognosis10.3934/mbe.20212961551-0018https://doaj.org/article/0d29a33c30ea4b558df607fdd33217762021-06-01T00:00:00Zhttps://www.aimspress.com/article/doi/10.3934/mbe.2021296?viewType=HTMLhttps://doaj.org/toc/1551-0018Background: Pancreatic adenocarcinoma (PAAD) is one of the most common malignant tumors with high mortality rates and a poor prognosis. There is an urgent need to determine the molecular mechanism of PAAD tumorigenesis and identify promising biomarkers for the diagnosis and targeted therapy of the disease. Methods: Three GEO datasets (GSE62165, GSE15471 and GSE62452) were analyzed to obtain differentially expressed genes (DEGs). The PPI networks and hub genes were identified through the STRING database and MCODE plugin in Cytoscape software. GO and KEGG enrichment pathways were analyzed by the DAVID database. The GEPIA database was utilized to estimate the prognostic value of hub genes. Furthermore, the roles of MMP14 and COL12A1 in immune infiltration and tumor-immune interaction and their biological functions in PAAD were explored by TIMER, TISIDB, GeneMANIA, Metascape and GSEA. Results: A total of 209 common DEGs in the three datasets were obtained. GO function analysis showed that the 209 DEGs were significantly enriched in calcium ion binding, serine-type endopeptidase activity, integrin binding, extracellular matrix structural constituent and collagen binding. KEGG pathway analysis showed that DEGs were mainly enriched in focal adhesion, protein digestion and absorption and ECM-receptor interaction. The 14 genes with the highest degree of connectivity were defined as the hub genes of PAAD development. GEPIA revealed that PAAD patients with upregulated MMP14 and COL12A1 expression had poor prognoses. In addition, TIMER analysis revealed that MMP14 and COL12A1 were closely associated with the infiltration levels of macrophages, neutrophils and dendritic cells in PAAD. TISIDB revealed that MMP14 was strongly positively correlated with CD276, TNFSF4, CD70 and TNFSF9, while COL12A1 was strongly positively correlated with TNFSF4, CD276, ENTPD1 and CD70. GSEA revealed that MMP14 and COL12A1 were significantly enriched in epithelial mesenchymal transition, extracellular matrix receptor interaction, apical junction, and focal adhesion in PAAD development. Conclusions: Our study revealed that overexpression of MMP14 and COL12A1 is significantly correlated with PAAD patient poor prognosis. MMP14 and COL12A1 participate in regulating tumor immune interactions and might become promising biomarkers for PAAD.Yuexian LiZhou SuBiwei Wei Mengbin QinZhihai Liang AIMS Pressarticlepancreatic adenocarcinomammp14col12a1prognosisbiomarkerbioinformatics analysisBiotechnologyTP248.13-248.65MathematicsQA1-939ENMathematical Biosciences and Engineering, Vol 18, Iss 5, Pp 5921-5942 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pancreatic adenocarcinoma mmp14 col12a1 prognosis biomarker bioinformatics analysis Biotechnology TP248.13-248.65 Mathematics QA1-939
spellingShingle	pancreatic adenocarcinoma mmp14 col12a1 prognosis biomarker bioinformatics analysis Biotechnology TP248.13-248.65 Mathematics QA1-939 Yuexian Li Zhou Su Biwei Wei Mengbin Qin Zhihai Liang Bioinformatics analysis identified MMP14 and COL12A1 as immune-related biomarkers associated with pancreatic adenocarcinoma prognosis
description	Background: Pancreatic adenocarcinoma (PAAD) is one of the most common malignant tumors with high mortality rates and a poor prognosis. There is an urgent need to determine the molecular mechanism of PAAD tumorigenesis and identify promising biomarkers for the diagnosis and targeted therapy of the disease. Methods: Three GEO datasets (GSE62165, GSE15471 and GSE62452) were analyzed to obtain differentially expressed genes (DEGs). The PPI networks and hub genes were identified through the STRING database and MCODE plugin in Cytoscape software. GO and KEGG enrichment pathways were analyzed by the DAVID database. The GEPIA database was utilized to estimate the prognostic value of hub genes. Furthermore, the roles of MMP14 and COL12A1 in immune infiltration and tumor-immune interaction and their biological functions in PAAD were explored by TIMER, TISIDB, GeneMANIA, Metascape and GSEA. Results: A total of 209 common DEGs in the three datasets were obtained. GO function analysis showed that the 209 DEGs were significantly enriched in calcium ion binding, serine-type endopeptidase activity, integrin binding, extracellular matrix structural constituent and collagen binding. KEGG pathway analysis showed that DEGs were mainly enriched in focal adhesion, protein digestion and absorption and ECM-receptor interaction. The 14 genes with the highest degree of connectivity were defined as the hub genes of PAAD development. GEPIA revealed that PAAD patients with upregulated MMP14 and COL12A1 expression had poor prognoses. In addition, TIMER analysis revealed that MMP14 and COL12A1 were closely associated with the infiltration levels of macrophages, neutrophils and dendritic cells in PAAD. TISIDB revealed that MMP14 was strongly positively correlated with CD276, TNFSF4, CD70 and TNFSF9, while COL12A1 was strongly positively correlated with TNFSF4, CD276, ENTPD1 and CD70. GSEA revealed that MMP14 and COL12A1 were significantly enriched in epithelial mesenchymal transition, extracellular matrix receptor interaction, apical junction, and focal adhesion in PAAD development. Conclusions: Our study revealed that overexpression of MMP14 and COL12A1 is significantly correlated with PAAD patient poor prognosis. MMP14 and COL12A1 participate in regulating tumor immune interactions and might become promising biomarkers for PAAD.
format	article
author	Yuexian Li Zhou Su Biwei Wei Mengbin Qin Zhihai Liang
author_facet	Yuexian Li Zhou Su Biwei Wei Mengbin Qin Zhihai Liang
author_sort	Yuexian Li
title	Bioinformatics analysis identified MMP14 and COL12A1 as immune-related biomarkers associated with pancreatic adenocarcinoma prognosis
title_short	Bioinformatics analysis identified MMP14 and COL12A1 as immune-related biomarkers associated with pancreatic adenocarcinoma prognosis
title_full	Bioinformatics analysis identified MMP14 and COL12A1 as immune-related biomarkers associated with pancreatic adenocarcinoma prognosis
title_fullStr	Bioinformatics analysis identified MMP14 and COL12A1 as immune-related biomarkers associated with pancreatic adenocarcinoma prognosis
title_full_unstemmed	Bioinformatics analysis identified MMP14 and COL12A1 as immune-related biomarkers associated with pancreatic adenocarcinoma prognosis
title_sort	bioinformatics analysis identified mmp14 and col12a1 as immune-related biomarkers associated with pancreatic adenocarcinoma prognosis
publisher	AIMS Press
publishDate	2021
url	https://doaj.org/article/0d29a33c30ea4b558df607fdd3321776
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_version_	1718441268185399296

Bioinformatics analysis identified MMP14 and COL12A1 as immune-related biomarkers associated with pancreatic adenocarcinoma prognosis

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