Cargando…

The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis

The tumor microenvironment (TME) plays a critical regulatory role in bladder cancer (BLCA) progression and metastasis. Epithelial-mesenchymal transition (EMT) presents as an essential mechanism of tumor invasion and metastasis. Accumulating pieces of evidence indicated that several microenvironmenta...

Descripción completa

Detalles Bibliográficos
Autores principales: Du, YiHeng, Miao, WenHao, Jiang, Xiang, Cao, Jin, Wang, Bo, Wang, Yi, Yu, Jiang, Wang, XiZhi, Liu, HaiTao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209417/
https://www.ncbi.nlm.nih.gov/pubmed/34150647
http://dx.doi.org/10.3389/fonc.2021.683951
_version_ 1783709125013667840
author Du, YiHeng
Miao, WenHao
Jiang, Xiang
Cao, Jin
Wang, Bo
Wang, Yi
Yu, Jiang
Wang, XiZhi
Liu, HaiTao
author_facet Du, YiHeng
Miao, WenHao
Jiang, Xiang
Cao, Jin
Wang, Bo
Wang, Yi
Yu, Jiang
Wang, XiZhi
Liu, HaiTao
author_sort Du, YiHeng
collection PubMed
description The tumor microenvironment (TME) plays a critical regulatory role in bladder cancer (BLCA) progression and metastasis. Epithelial-mesenchymal transition (EMT) presents as an essential mechanism of tumor invasion and metastasis. Accumulating pieces of evidence indicated that several microenvironmental factors, including fibroblasts, endothelial, and immune cells, induced EMT in tumor cells. As a hallmark gene of the EMT process, calumenin (CALU) was previously reported to directly impact cancer metastasis. However, the functions and molecular mechanisms of CALU have been rarely reported in BLCA. By multi-omics bioinformatics analysis of 408 TCGA BLCA patients, we demonstrated that CALU was an independent risk factor for BLCA outcome. Subsequently, we verified the correlation of CALU with cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells. The results suggested a positive correlation of CALU with CAFs, CD8+ T cells and macrophages. Also, CALU was significantly associated with multiple immune checkpoint-related genes, which ultimately influenced patients’ responsiveness to immunotherapy. Further, we found that the impact of CALU on BLCA prognosis might also be correlated with gene mutations and ferroptosis. Finally, we validated the roles of CALU by single-cell RNA sequencing, PCR and immunohistochemistry. In conclusion, we found that CALU affected BLCA prognosis associated with multiple mechanisms, including TME remodeling, gene mutation and ferroptosis. Further studies on CALU may provide new targets for BLCA immunotherapy and precision medicine.
format Online
Article
Text
id pubmed-8209417
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-82094172021-06-18 The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis Du, YiHeng Miao, WenHao Jiang, Xiang Cao, Jin Wang, Bo Wang, Yi Yu, Jiang Wang, XiZhi Liu, HaiTao Front Oncol Oncology The tumor microenvironment (TME) plays a critical regulatory role in bladder cancer (BLCA) progression and metastasis. Epithelial-mesenchymal transition (EMT) presents as an essential mechanism of tumor invasion and metastasis. Accumulating pieces of evidence indicated that several microenvironmental factors, including fibroblasts, endothelial, and immune cells, induced EMT in tumor cells. As a hallmark gene of the EMT process, calumenin (CALU) was previously reported to directly impact cancer metastasis. However, the functions and molecular mechanisms of CALU have been rarely reported in BLCA. By multi-omics bioinformatics analysis of 408 TCGA BLCA patients, we demonstrated that CALU was an independent risk factor for BLCA outcome. Subsequently, we verified the correlation of CALU with cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells. The results suggested a positive correlation of CALU with CAFs, CD8+ T cells and macrophages. Also, CALU was significantly associated with multiple immune checkpoint-related genes, which ultimately influenced patients’ responsiveness to immunotherapy. Further, we found that the impact of CALU on BLCA prognosis might also be correlated with gene mutations and ferroptosis. Finally, we validated the roles of CALU by single-cell RNA sequencing, PCR and immunohistochemistry. In conclusion, we found that CALU affected BLCA prognosis associated with multiple mechanisms, including TME remodeling, gene mutation and ferroptosis. Further studies on CALU may provide new targets for BLCA immunotherapy and precision medicine. Frontiers Media S.A. 2021-06-03 /pmc/articles/PMC8209417/ /pubmed/34150647 http://dx.doi.org/10.3389/fonc.2021.683951 Text en Copyright © 2021 Du, Miao, Jiang, Cao, Wang, Wang, Yu, Wang 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 Oncology
Du, YiHeng
Miao, WenHao
Jiang, Xiang
Cao, Jin
Wang, Bo
Wang, Yi
Yu, Jiang
Wang, XiZhi
Liu, HaiTao
The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis
title The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis
title_full The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis
title_fullStr The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis
title_full_unstemmed The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis
title_short The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis
title_sort epithelial to mesenchymal transition related gene calumenin is an adverse prognostic factor of bladder cancer correlated with tumor microenvironment remodeling, gene mutation, and ferroptosis
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209417/
https://www.ncbi.nlm.nih.gov/pubmed/34150647
http://dx.doi.org/10.3389/fonc.2021.683951
work_keys_str_mv AT duyiheng theepithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT miaowenhao theepithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT jiangxiang theepithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT caojin theepithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT wangbo theepithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT wangyi theepithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT yujiang theepithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT wangxizhi theepithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT liuhaitao theepithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT duyiheng epithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT miaowenhao epithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT jiangxiang epithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT caojin epithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT wangbo epithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT wangyi epithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT yujiang epithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT wangxizhi epithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis
AT liuhaitao epithelialtomesenchymaltransitionrelatedgenecalumeninisanadverseprognosticfactorofbladdercancercorrelatedwithtumormicroenvironmentremodelinggenemutationandferroptosis