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Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas
BACKGROUND: Siglec15 is rising as a promising immunotherapeutic target in bladder, breast, gastric, and pancreatic cancers. The aim of the present study is to explore the prognostic value and immunotherapeutic possibilities of Siglec15 in gliomas using bioinformatics and clinicopathological methods....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266207/ https://www.ncbi.nlm.nih.gov/pubmed/37325664 http://dx.doi.org/10.3389/fimmu.2023.1065062 |
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author | Wang, Jinchao Xu, Linzong Ding, Qian Li, Xiaoru Wang, Kai Xu, Shangchen Liu, Bin |
author_facet | Wang, Jinchao Xu, Linzong Ding, Qian Li, Xiaoru Wang, Kai Xu, Shangchen Liu, Bin |
author_sort | Wang, Jinchao |
collection | PubMed |
description | BACKGROUND: Siglec15 is rising as a promising immunotherapeutic target in bladder, breast, gastric, and pancreatic cancers. The aim of the present study is to explore the prognostic value and immunotherapeutic possibilities of Siglec15 in gliomas using bioinformatics and clinicopathological methods. METHODS: The bioinformatics approach was used to examine Siglec15 mRNA expression in gliomas based on TCGA, CGGA, and GEO datasets. Then, the predictive value of Siglec15 expression on progression-free survival time (PFST) and overall survival time (OST) in glioma patients was comprehensively described.The TCGA database was screened for differentially expressed genes (DEGs) between the high and low Siglec15 expression groups, and enrichment analysis of the DEGs was performed. The Siglec15 protein expression and its prognostic impact in 92 glioma samples were explored using immunohistochemistry Next, the relationships between Siglec15 expression and infiltrating immune cells, immune regulators and multiple immune checkpoints were analysed. RESULTS: Bioinformatics analyses showed that high Siglec15 levels predicted poor clinical prognosis and adverse recurrence time in glioma patients. In the immunohistochemical study serving as a validation set, Siglec15 protein overexpression was found in 33.3% (10/30) of WHO grade II, 56% (14/25) of WHO grade III, and 70.3% (26/37) of WHO grade IV gliomas respectively. Siglec15 protein overexpression was also found to be an independent prognostic indicator detrimental to the PFST and OST of glioma patients. Enrichment analysis showed that the DEGs were mainly involved in pathways associated with immune function, including leukocyte transendothelial migration, focal adhesion, ECM receptor interaction, and T-cell receptor signaling pathways. In addition, high Siglec15 expression was related to M2 tumor-associated macrophages (TAMs), N2 tumor-infiltrating neutrophils, suppressive tumor immune microenvironment, and multiple immune checkpoint molecules. Immunofluorescence analysis confirmed the colocalization of Siglec15 and CD163 on TAMs. CONCLUSION: Siglec15 overexpression is common in gliomas and predicts an adverse recurrence time and overall survival time. Siglec15 is a potential target for immunotherapy and a potential TAMs regulator that is involved in the suppressed immunomicroenvironment in gliomas. |
format | Online Article Text |
id | pubmed-10266207 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102662072023-06-15 Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas Wang, Jinchao Xu, Linzong Ding, Qian Li, Xiaoru Wang, Kai Xu, Shangchen Liu, Bin Front Immunol Immunology BACKGROUND: Siglec15 is rising as a promising immunotherapeutic target in bladder, breast, gastric, and pancreatic cancers. The aim of the present study is to explore the prognostic value and immunotherapeutic possibilities of Siglec15 in gliomas using bioinformatics and clinicopathological methods. METHODS: The bioinformatics approach was used to examine Siglec15 mRNA expression in gliomas based on TCGA, CGGA, and GEO datasets. Then, the predictive value of Siglec15 expression on progression-free survival time (PFST) and overall survival time (OST) in glioma patients was comprehensively described.The TCGA database was screened for differentially expressed genes (DEGs) between the high and low Siglec15 expression groups, and enrichment analysis of the DEGs was performed. The Siglec15 protein expression and its prognostic impact in 92 glioma samples were explored using immunohistochemistry Next, the relationships between Siglec15 expression and infiltrating immune cells, immune regulators and multiple immune checkpoints were analysed. RESULTS: Bioinformatics analyses showed that high Siglec15 levels predicted poor clinical prognosis and adverse recurrence time in glioma patients. In the immunohistochemical study serving as a validation set, Siglec15 protein overexpression was found in 33.3% (10/30) of WHO grade II, 56% (14/25) of WHO grade III, and 70.3% (26/37) of WHO grade IV gliomas respectively. Siglec15 protein overexpression was also found to be an independent prognostic indicator detrimental to the PFST and OST of glioma patients. Enrichment analysis showed that the DEGs were mainly involved in pathways associated with immune function, including leukocyte transendothelial migration, focal adhesion, ECM receptor interaction, and T-cell receptor signaling pathways. In addition, high Siglec15 expression was related to M2 tumor-associated macrophages (TAMs), N2 tumor-infiltrating neutrophils, suppressive tumor immune microenvironment, and multiple immune checkpoint molecules. Immunofluorescence analysis confirmed the colocalization of Siglec15 and CD163 on TAMs. CONCLUSION: Siglec15 overexpression is common in gliomas and predicts an adverse recurrence time and overall survival time. Siglec15 is a potential target for immunotherapy and a potential TAMs regulator that is involved in the suppressed immunomicroenvironment in gliomas. Frontiers Media S.A. 2023-05-30 /pmc/articles/PMC10266207/ /pubmed/37325664 http://dx.doi.org/10.3389/fimmu.2023.1065062 Text en Copyright © 2023 Wang, Xu, Ding, Li, Wang, Xu 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 | Immunology Wang, Jinchao Xu, Linzong Ding, Qian Li, Xiaoru Wang, Kai Xu, Shangchen Liu, Bin Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas |
title | Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas |
title_full | Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas |
title_fullStr | Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas |
title_full_unstemmed | Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas |
title_short | Siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas |
title_sort | siglec15 is a prognostic indicator and a potential tumor-related macrophage regulator that is involved in the suppressive immunomicroenvironment in gliomas |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10266207/ https://www.ncbi.nlm.nih.gov/pubmed/37325664 http://dx.doi.org/10.3389/fimmu.2023.1065062 |
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