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ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors

BACKGROUND: Integrin Subunit Alpha 5 (ITGA5), belongs to the integrin alpha chain family, is vital for promoting cancer cell invasion, metastasis. However, the correlation between ITGA5 expression and immune infiltration in gastrointestinal tumors remain unclear. METHODS: The expression level of ITG...

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Autores principales: Zhu, Hai, Wang, Gang, Zhu, Haixing, Xu, Aman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953822/
https://www.ncbi.nlm.nih.gov/pubmed/33711961
http://dx.doi.org/10.1186/s12885-021-07996-1
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author Zhu, Hai
Wang, Gang
Zhu, Haixing
Xu, Aman
author_facet Zhu, Hai
Wang, Gang
Zhu, Haixing
Xu, Aman
author_sort Zhu, Hai
collection PubMed
description BACKGROUND: Integrin Subunit Alpha 5 (ITGA5), belongs to the integrin alpha chain family, is vital for promoting cancer cell invasion, metastasis. However, the correlation between ITGA5 expression and immune infiltration in gastrointestinal tumors remain unclear. METHODS: The expression level of ITGA5 was detected by Oncomine and Tumor Immune Estimation Resource (TIMER). The association between ITGA5 and prognosis of patients was identified by Kaplan–Meier plotter, Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and PrognoScan. We evaluated the correlation between ITGA5 expression and immune infiltrating level via TIMER. Besides, TIMER, immunohistochemistry (IHC) staining and western blot were used to explore correlations between ITGA5 expression and markers of immune infiltrates cells. Furthermore, we constructed protein-protein interaction (PPI) network and performed functional enrichment by GeneMANIA and Metascape. RESULTS: ITGA5 was generally overexpressed and correlated with worse prognosis in multiple types of gastrointestinal tumors. In addition, ITGA5 expression level was significantly associated with tumor purity and immune infiltration levels of different immune cells in gastrointestinal tumors. Interestingly, immune markers for monocytes, tumor - associated macrophages (TAMs), macrophages 2 (M2) cells and T-helper 2 (Th2) cells were found to be significantly and positively correlated with ITGA5 expression levels in colon and gastric cancer. Results from IHC staining and western blot further proved that markers of Th2 and M2 cell were significantly increased in gastric cancer patients with high ITGA5 expression levels. Lastly, interaction network and function enrichment analysis revealed ITGA5 was mainly involved in “integrin mediated signaling pathway”, “leukocyte migration”, “cell-substrate adhesion”. CONCLUTIONS: Our study demonstrated that ITGA5 may act as an essential regulator of tumor immune cell infiltration and a valuable prognostic biomarker in gastrointestinal tumors. Additional work is needed to fully elucidate the underlying mechanisms behind these observations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-07996-1.
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spelling pubmed-79538222021-03-15 ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors Zhu, Hai Wang, Gang Zhu, Haixing Xu, Aman BMC Cancer Research Article BACKGROUND: Integrin Subunit Alpha 5 (ITGA5), belongs to the integrin alpha chain family, is vital for promoting cancer cell invasion, metastasis. However, the correlation between ITGA5 expression and immune infiltration in gastrointestinal tumors remain unclear. METHODS: The expression level of ITGA5 was detected by Oncomine and Tumor Immune Estimation Resource (TIMER). The association between ITGA5 and prognosis of patients was identified by Kaplan–Meier plotter, Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and PrognoScan. We evaluated the correlation between ITGA5 expression and immune infiltrating level via TIMER. Besides, TIMER, immunohistochemistry (IHC) staining and western blot were used to explore correlations between ITGA5 expression and markers of immune infiltrates cells. Furthermore, we constructed protein-protein interaction (PPI) network and performed functional enrichment by GeneMANIA and Metascape. RESULTS: ITGA5 was generally overexpressed and correlated with worse prognosis in multiple types of gastrointestinal tumors. In addition, ITGA5 expression level was significantly associated with tumor purity and immune infiltration levels of different immune cells in gastrointestinal tumors. Interestingly, immune markers for monocytes, tumor - associated macrophages (TAMs), macrophages 2 (M2) cells and T-helper 2 (Th2) cells were found to be significantly and positively correlated with ITGA5 expression levels in colon and gastric cancer. Results from IHC staining and western blot further proved that markers of Th2 and M2 cell were significantly increased in gastric cancer patients with high ITGA5 expression levels. Lastly, interaction network and function enrichment analysis revealed ITGA5 was mainly involved in “integrin mediated signaling pathway”, “leukocyte migration”, “cell-substrate adhesion”. CONCLUTIONS: Our study demonstrated that ITGA5 may act as an essential regulator of tumor immune cell infiltration and a valuable prognostic biomarker in gastrointestinal tumors. Additional work is needed to fully elucidate the underlying mechanisms behind these observations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-07996-1. BioMed Central 2021-03-12 /pmc/articles/PMC7953822/ /pubmed/33711961 http://dx.doi.org/10.1186/s12885-021-07996-1 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Zhu, Hai
Wang, Gang
Zhu, Haixing
Xu, Aman
ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors
title ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors
title_full ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors
title_fullStr ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors
title_full_unstemmed ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors
title_short ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors
title_sort itga5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953822/
https://www.ncbi.nlm.nih.gov/pubmed/33711961
http://dx.doi.org/10.1186/s12885-021-07996-1
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