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Clinical value of M1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation

Background: Tumor microenvironment (TME) takes a non-negligible role in the progression and metastasis of bladder urothelial carcinoma (BLCA) and tumor development could be inhibited by macrophage M1 in TME. The role of macrophage M1-related genes in BLCA adjuvant therapy has not been studied well....

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Autores principales: Yu, Yang, Huang, Yuexi, Li, Chen, Ou, Santao, Xu, Chaojie, Kang, Zhengjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709473/
https://www.ncbi.nlm.nih.gov/pubmed/36468020
http://dx.doi.org/10.3389/fgene.2022.1047004
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author Yu, Yang
Huang, Yuexi
Li, Chen
Ou, Santao
Xu, Chaojie
Kang, Zhengjun
author_facet Yu, Yang
Huang, Yuexi
Li, Chen
Ou, Santao
Xu, Chaojie
Kang, Zhengjun
author_sort Yu, Yang
collection PubMed
description Background: Tumor microenvironment (TME) takes a non-negligible role in the progression and metastasis of bladder urothelial carcinoma (BLCA) and tumor development could be inhibited by macrophage M1 in TME. The role of macrophage M1-related genes in BLCA adjuvant therapy has not been studied well. Methods: CIBERSOR algorithm was applied for identification tumor-infiltrating immune cells (TICs) subtypes of subjects from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. We identified potential modules of M1 macrophages by weighted gene co-expression network analysis (WGCNA). Nomogram was determined by one-way Cox regression and lasso regression analysis for M1 macrophage genes. The data from GEO are taken to verify the models externally. Kaplan-Meier and receiver operating characteristic (ROC) curves validated prognostic value of M1 macrophage genes. Finally, we divided patients into the low-risk group (LRG) and the high-risk group (HRG) based on the median risk score (RS), and the predictive value of RS in patients with BLCA immunotherapy and chemotherapy was investigated. Bladder cancer (T24, 5637, and BIU-87) and bladder uroepithelial cell line (SV-HUC-1) were used for in vitro validation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to validate the associated genes mRNA level. Results: 111 macrophage M1-related genes were identified using WGCNA. RS model containing three prognostically significant M1 macrophage-associated genes (FBXO6, OAS1, and TMEM229B) was formed by multiple Cox analysis, and a polygenic risk model and a comprehensive prognostic line plot was developed. The calibration curve clarified RS was a good predictor of prognosis. Patients in the LRG were more suitable for programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte associate protein-4 (CTLA4) combination immunotherapy. Finally, chemotherapeutic drug models showed patients in the LRG were more sensitive to gemcitabine and mitomycin. RT-qPCR result elucidated the upregulation of FBXO6, TMEM229B, and downregulation of OAS1 in BLCA cell lines. Conclusion: A predictive model based on M1 macrophage-related genes can help guide us in the treatment of BLCA.
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spelling pubmed-97094732022-12-01 Clinical value of M1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation Yu, Yang Huang, Yuexi Li, Chen Ou, Santao Xu, Chaojie Kang, Zhengjun Front Genet Genetics Background: Tumor microenvironment (TME) takes a non-negligible role in the progression and metastasis of bladder urothelial carcinoma (BLCA) and tumor development could be inhibited by macrophage M1 in TME. The role of macrophage M1-related genes in BLCA adjuvant therapy has not been studied well. Methods: CIBERSOR algorithm was applied for identification tumor-infiltrating immune cells (TICs) subtypes of subjects from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. We identified potential modules of M1 macrophages by weighted gene co-expression network analysis (WGCNA). Nomogram was determined by one-way Cox regression and lasso regression analysis for M1 macrophage genes. The data from GEO are taken to verify the models externally. Kaplan-Meier and receiver operating characteristic (ROC) curves validated prognostic value of M1 macrophage genes. Finally, we divided patients into the low-risk group (LRG) and the high-risk group (HRG) based on the median risk score (RS), and the predictive value of RS in patients with BLCA immunotherapy and chemotherapy was investigated. Bladder cancer (T24, 5637, and BIU-87) and bladder uroepithelial cell line (SV-HUC-1) were used for in vitro validation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to validate the associated genes mRNA level. Results: 111 macrophage M1-related genes were identified using WGCNA. RS model containing three prognostically significant M1 macrophage-associated genes (FBXO6, OAS1, and TMEM229B) was formed by multiple Cox analysis, and a polygenic risk model and a comprehensive prognostic line plot was developed. The calibration curve clarified RS was a good predictor of prognosis. Patients in the LRG were more suitable for programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte associate protein-4 (CTLA4) combination immunotherapy. Finally, chemotherapeutic drug models showed patients in the LRG were more sensitive to gemcitabine and mitomycin. RT-qPCR result elucidated the upregulation of FBXO6, TMEM229B, and downregulation of OAS1 in BLCA cell lines. Conclusion: A predictive model based on M1 macrophage-related genes can help guide us in the treatment of BLCA. Frontiers Media S.A. 2022-11-16 /pmc/articles/PMC9709473/ /pubmed/36468020 http://dx.doi.org/10.3389/fgene.2022.1047004 Text en Copyright © 2022 Yu, Huang, Li, Ou, Xu and Kang. 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 Genetics
Yu, Yang
Huang, Yuexi
Li, Chen
Ou, Santao
Xu, Chaojie
Kang, Zhengjun
Clinical value of M1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation
title Clinical value of M1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation
title_full Clinical value of M1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation
title_fullStr Clinical value of M1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation
title_full_unstemmed Clinical value of M1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation
title_short Clinical value of M1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation
title_sort clinical value of m1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709473/
https://www.ncbi.nlm.nih.gov/pubmed/36468020
http://dx.doi.org/10.3389/fgene.2022.1047004
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