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Systematical analysis of ferroptosis regulators and identification of GCLM as a tumor promotor and immunological biomarker in bladder cancer

Bladder cancer (BCa) is a life-threaten disease with an increasing incidence with age, and immunotherapy has become an important treatment for BCa, while the efficiency of the immune system declines with age. It is vital to reveal the mechanisms of tumor immune microenvironment (TIME) and identify n...

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Autores principales: Wang, Song, Wang, He, Zhu, Shaoxing, Li, Fangyin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9638099/
https://www.ncbi.nlm.nih.gov/pubmed/36353567
http://dx.doi.org/10.3389/fonc.2022.1040892
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author Wang, Song
Wang, He
Zhu, Shaoxing
Li, Fangyin
author_facet Wang, Song
Wang, He
Zhu, Shaoxing
Li, Fangyin
author_sort Wang, Song
collection PubMed
description Bladder cancer (BCa) is a life-threaten disease with an increasing incidence with age, and immunotherapy has become an important treatment for BCa, while the efficiency of the immune system declines with age. It is vital to reveal the mechanisms of tumor immune microenvironment (TIME) and identify novel immunotherapy targets for BCa. Through analyzing the RNA-seq of TCGA-BLCA cohort, we distinguished two ferroptosis-related BCa clusters, and we discovered that in comparation with cluster 2, the cluster 1 BCa patients showed higher PD-L1 expression, more unfavorable overall survival and higher tumor stage and grade. XCELL analyses showed that higher level of Th2 cell and Myeloid dendritic cell were enriched in cluster 1, while NK T cell was enriched in cluster 2, and TIDE analysis revealed that cluster 2 was more sensitive to immunotherapy than cluster 1. GSEA analysis implied that Toll-like signaling pathway and JAK_STAT signaling pathway were significantly enriched in cluster 1. Subsequently, through performing bioinformatic analysis and cell experiments, we demonstrated that GCLM is overexpressed in BCa and indicates dismal prognosis, and knockdown of GCLM can significantly suppress the colony formation ability of BCa cells. Furthermore, we also found that GCLM might be correlated with immune infiltration in BCa, and can serve as a tumor promotor and immunological biomarker in BCa, our research showed the vital roles of ferroptosis regulators in TIME of BCa, and GCLM is a latent therapeutic target for cancer immunotherapy.
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spelling pubmed-96380992022-11-08 Systematical analysis of ferroptosis regulators and identification of GCLM as a tumor promotor and immunological biomarker in bladder cancer Wang, Song Wang, He Zhu, Shaoxing Li, Fangyin Front Oncol Oncology Bladder cancer (BCa) is a life-threaten disease with an increasing incidence with age, and immunotherapy has become an important treatment for BCa, while the efficiency of the immune system declines with age. It is vital to reveal the mechanisms of tumor immune microenvironment (TIME) and identify novel immunotherapy targets for BCa. Through analyzing the RNA-seq of TCGA-BLCA cohort, we distinguished two ferroptosis-related BCa clusters, and we discovered that in comparation with cluster 2, the cluster 1 BCa patients showed higher PD-L1 expression, more unfavorable overall survival and higher tumor stage and grade. XCELL analyses showed that higher level of Th2 cell and Myeloid dendritic cell were enriched in cluster 1, while NK T cell was enriched in cluster 2, and TIDE analysis revealed that cluster 2 was more sensitive to immunotherapy than cluster 1. GSEA analysis implied that Toll-like signaling pathway and JAK_STAT signaling pathway were significantly enriched in cluster 1. Subsequently, through performing bioinformatic analysis and cell experiments, we demonstrated that GCLM is overexpressed in BCa and indicates dismal prognosis, and knockdown of GCLM can significantly suppress the colony formation ability of BCa cells. Furthermore, we also found that GCLM might be correlated with immune infiltration in BCa, and can serve as a tumor promotor and immunological biomarker in BCa, our research showed the vital roles of ferroptosis regulators in TIME of BCa, and GCLM is a latent therapeutic target for cancer immunotherapy. Frontiers Media S.A. 2022-10-24 /pmc/articles/PMC9638099/ /pubmed/36353567 http://dx.doi.org/10.3389/fonc.2022.1040892 Text en Copyright © 2022 Wang, Wang, Zhu and Li 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 Oncology
Wang, Song
Wang, He
Zhu, Shaoxing
Li, Fangyin
Systematical analysis of ferroptosis regulators and identification of GCLM as a tumor promotor and immunological biomarker in bladder cancer
title Systematical analysis of ferroptosis regulators and identification of GCLM as a tumor promotor and immunological biomarker in bladder cancer
title_full Systematical analysis of ferroptosis regulators and identification of GCLM as a tumor promotor and immunological biomarker in bladder cancer
title_fullStr Systematical analysis of ferroptosis regulators and identification of GCLM as a tumor promotor and immunological biomarker in bladder cancer
title_full_unstemmed Systematical analysis of ferroptosis regulators and identification of GCLM as a tumor promotor and immunological biomarker in bladder cancer
title_short Systematical analysis of ferroptosis regulators and identification of GCLM as a tumor promotor and immunological biomarker in bladder cancer
title_sort systematical analysis of ferroptosis regulators and identification of gclm as a tumor promotor and immunological biomarker in bladder cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9638099/
https://www.ncbi.nlm.nih.gov/pubmed/36353567
http://dx.doi.org/10.3389/fonc.2022.1040892
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