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Macrophage M2 Co-expression Factors Correlate With the Immune Microenvironment and Predict Outcome of Renal Clear Cell Carcinoma
Purpose: In the tumor microenvironment, the functional differences among various tumor-associated macrophages (TAM) are not completely clear. Tumor-associated macrophages are thought to promote the progression of cancer. This article focuses on exploring M2 macrophage-related factors and behaviors o...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938896/ https://www.ncbi.nlm.nih.gov/pubmed/33692827 http://dx.doi.org/10.3389/fgene.2021.615655 |
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author | Wang, Yutao Yan, Kexin Lin, Jiaxing Li, Jun Bi, Jianbin |
author_facet | Wang, Yutao Yan, Kexin Lin, Jiaxing Li, Jun Bi, Jianbin |
author_sort | Wang, Yutao |
collection | PubMed |
description | Purpose: In the tumor microenvironment, the functional differences among various tumor-associated macrophages (TAM) are not completely clear. Tumor-associated macrophages are thought to promote the progression of cancer. This article focuses on exploring M2 macrophage-related factors and behaviors of renal clear cell carcinoma. Method: We obtained renal clear cell carcinoma data from TCGA-KIRC-FPKM, GSE8050, GSE12606, GSE14762, and GSE3689. We used the “Cibersort” algorithm to calculate type M2 macrophage proportions among 22 types of immune cells. M2 macrophage-related co-expression module genes were selected using weighted gene co-expression network analysis (WGCNA). A renal clear cell carcinoma prognosis risk score was built based on M2 macrophage-related factors. The ROC curve and Kaplan–Meier analysis were performed to evacuate the risk score in various subgroups. The Pearson test was used to calculate correlations among M2 macrophage-related genes, clinical phenotype, immune phenotype, and tumor mutation burden (TMB). We measured differences in co-expression of genes at the protein level in clear renal cell carcinoma tissues. Results: There were six M2 macrophage co-expressed genes (F13A1, FUCA1, SDCBP, VSIG4, HLA-E, TAP2) related to infiltration of M2 macrophages; these were enriched in neutrophil activation and involved in immune responses, antigen processing, and presentation of exogenous peptide antigen via MHC class I. M2-related factor frequencies were robust biomarkers for predicting the renal clear cell carcinoma patient clinical phenotype and immune microenvironment. The Cox regression model, built based on M2 macrophage-related factors, showed a close prognostic correlation (AUC = 0.78). The M2 macrophage-related prognosis model also performed well in various subgroups. Using western blotting, we found that VSIG4 protein expression levels were higher in clear renal cell carcinoma tissues than in normal tissues. Conclusion: These co-expressed genes were most related to the M2 macrophage phenotype. They correlated with the immune microenvironment and predicted outcomes of renal clear cell carcinoma. These co-expressed genes and the biological processes associated with them might provide the basis for new strategies to intervene via chemotaxis of M2 macrophages. |
format | Online Article Text |
id | pubmed-7938896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79388962021-03-09 Macrophage M2 Co-expression Factors Correlate With the Immune Microenvironment and Predict Outcome of Renal Clear Cell Carcinoma Wang, Yutao Yan, Kexin Lin, Jiaxing Li, Jun Bi, Jianbin Front Genet Genetics Purpose: In the tumor microenvironment, the functional differences among various tumor-associated macrophages (TAM) are not completely clear. Tumor-associated macrophages are thought to promote the progression of cancer. This article focuses on exploring M2 macrophage-related factors and behaviors of renal clear cell carcinoma. Method: We obtained renal clear cell carcinoma data from TCGA-KIRC-FPKM, GSE8050, GSE12606, GSE14762, and GSE3689. We used the “Cibersort” algorithm to calculate type M2 macrophage proportions among 22 types of immune cells. M2 macrophage-related co-expression module genes were selected using weighted gene co-expression network analysis (WGCNA). A renal clear cell carcinoma prognosis risk score was built based on M2 macrophage-related factors. The ROC curve and Kaplan–Meier analysis were performed to evacuate the risk score in various subgroups. The Pearson test was used to calculate correlations among M2 macrophage-related genes, clinical phenotype, immune phenotype, and tumor mutation burden (TMB). We measured differences in co-expression of genes at the protein level in clear renal cell carcinoma tissues. Results: There were six M2 macrophage co-expressed genes (F13A1, FUCA1, SDCBP, VSIG4, HLA-E, TAP2) related to infiltration of M2 macrophages; these were enriched in neutrophil activation and involved in immune responses, antigen processing, and presentation of exogenous peptide antigen via MHC class I. M2-related factor frequencies were robust biomarkers for predicting the renal clear cell carcinoma patient clinical phenotype and immune microenvironment. The Cox regression model, built based on M2 macrophage-related factors, showed a close prognostic correlation (AUC = 0.78). The M2 macrophage-related prognosis model also performed well in various subgroups. Using western blotting, we found that VSIG4 protein expression levels were higher in clear renal cell carcinoma tissues than in normal tissues. Conclusion: These co-expressed genes were most related to the M2 macrophage phenotype. They correlated with the immune microenvironment and predicted outcomes of renal clear cell carcinoma. These co-expressed genes and the biological processes associated with them might provide the basis for new strategies to intervene via chemotaxis of M2 macrophages. Frontiers Media S.A. 2021-02-22 /pmc/articles/PMC7938896/ /pubmed/33692827 http://dx.doi.org/10.3389/fgene.2021.615655 Text en Copyright © 2021 Wang, Yan, Lin, Li and Bi. http://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 | Genetics Wang, Yutao Yan, Kexin Lin, Jiaxing Li, Jun Bi, Jianbin Macrophage M2 Co-expression Factors Correlate With the Immune Microenvironment and Predict Outcome of Renal Clear Cell Carcinoma |
title | Macrophage M2 Co-expression Factors Correlate With the Immune Microenvironment and Predict Outcome of Renal Clear Cell Carcinoma |
title_full | Macrophage M2 Co-expression Factors Correlate With the Immune Microenvironment and Predict Outcome of Renal Clear Cell Carcinoma |
title_fullStr | Macrophage M2 Co-expression Factors Correlate With the Immune Microenvironment and Predict Outcome of Renal Clear Cell Carcinoma |
title_full_unstemmed | Macrophage M2 Co-expression Factors Correlate With the Immune Microenvironment and Predict Outcome of Renal Clear Cell Carcinoma |
title_short | Macrophage M2 Co-expression Factors Correlate With the Immune Microenvironment and Predict Outcome of Renal Clear Cell Carcinoma |
title_sort | macrophage m2 co-expression factors correlate with the immune microenvironment and predict outcome of renal clear cell carcinoma |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938896/ https://www.ncbi.nlm.nih.gov/pubmed/33692827 http://dx.doi.org/10.3389/fgene.2021.615655 |
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