Novel Ferroptosis-Related Multigene Prognostic Models for Patients with Bladder Cancer

Shun Zhang,&ast; Cheng Wang,&ast; Weimin Xia, Huangqi Duan, Subo Qian, Haibo Shen Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haib...

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Autores principales:	Zhang S, Wang C, Xia W, Duan H, Qian S, Shen H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	ferroptosis bladder cancer mibc nmibc prognosis gene signature Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8ae1ed9e6e20405691e4f730c8bcc659
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spelling	oai:doaj.org-article:8ae1ed9e6e20405691e4f730c8bcc6592021-11-23T18:43:01ZNovel Ferroptosis-Related Multigene Prognostic Models for Patients with Bladder Cancer1178-7074https://doaj.org/article/8ae1ed9e6e20405691e4f730c8bcc6592021-11-01T00:00:00Zhttps://www.dovepress.com/novel-ferroptosis-related-multigene-prognostic-models-for-patients-wit-peer-reviewed-fulltext-article-IJGMhttps://doaj.org/toc/1178-7074Shun Zhang,&ast; Cheng Wang,&ast; Weimin Xia, Huangqi Duan, Subo Qian, Haibo Shen Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haibo Shen;Subo Qian Tel +86-13651698392; +86-13761020575Fax +86-21-25078095Email shenhaibo@xinhuamed.com.cn; qiansubo@xinhuamed.com.cnObjective: Bladder cancer contributes to a serious disease burden in clinical settings. The characteristics and prognosis of patients with muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC) are distinctly different. The study aims to figure out the respective role of ferroptosis in MIBC and NMIBC and to construct ferroptosis-related gene signatures that could predict patients’ prognoses.Methods: A total of 608 MIBC and 414 NMIBC RNA-seq transcriptome data with intact clinical and follow-up information were downloaded from The Cancer Genome Atlas (TCGA), ArrayExpress, and Gene expression omnibus (GEO) database. Ferroptosis-related multigene prognostic models were constructed and externally validated, respectively, in MIBC and NMIBC. Further functional enrichment analyses were also performed to explicate the underlying mechanisms and the differences between the two bladder cancer subtypes.Results: In MIBC, a 7-gene signature for prognostic prediction was constructed. Patients were then divided into high-risk and low-risk groups according to the risk scores calculated by the 7-gene prognostic model. Patients in the high-risk group presented an impaired OS when compared with patients in the low-risk group both in the training cohort and validation cohort. Further functional analyses revealed distinctly different immune statuses between the two risk-stratification groups, speculating that exhausted immune cell function was a cause of the worst OS in the high-risk group. In NMIBC, 6 ferroptosis-related genes were identified that were significantly correlated with recurrence-free survival (RFS). Similarly, a 6-gene prognostic model was constructed and verified as an independent prognostic predictor for RFS. Functional analyses revealed significant differences in the expressions of nuclear division genes between the high-risk group and low-risk group.Conclusion: Two novel ferroptosis-related multigene prognostic models for, respectively, predicting OS in MIBC and RFS in NMIBC were identified in this study, which indicated ferroptosis played vital roles in the oncogenesis and development of MIBC and NMIBC.Keywords: ferroptosis, bladder cancer, MIBC, NMIBC, prognosis, gene signatureZhang SWang CXia WDuan HQian SShen HDove Medical Pressarticleferroptosisbladder cancermibcnmibcprognosisgene signatureMedicine (General)R5-920ENInternational Journal of General Medicine, Vol Volume 14, Pp 8651-8666 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ferroptosis bladder cancer mibc nmibc prognosis gene signature Medicine (General) R5-920
spellingShingle	ferroptosis bladder cancer mibc nmibc prognosis gene signature Medicine (General) R5-920 Zhang S Wang C Xia W Duan H Qian S Shen H Novel Ferroptosis-Related Multigene Prognostic Models for Patients with Bladder Cancer
description	Shun Zhang,&ast; Cheng Wang,&ast; Weimin Xia, Huangqi Duan, Subo Qian, Haibo Shen Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haibo Shen;Subo Qian Tel +86-13651698392; +86-13761020575Fax +86-21-25078095Email shenhaibo@xinhuamed.com.cn; qiansubo@xinhuamed.com.cnObjective: Bladder cancer contributes to a serious disease burden in clinical settings. The characteristics and prognosis of patients with muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC) are distinctly different. The study aims to figure out the respective role of ferroptosis in MIBC and NMIBC and to construct ferroptosis-related gene signatures that could predict patients’ prognoses.Methods: A total of 608 MIBC and 414 NMIBC RNA-seq transcriptome data with intact clinical and follow-up information were downloaded from The Cancer Genome Atlas (TCGA), ArrayExpress, and Gene expression omnibus (GEO) database. Ferroptosis-related multigene prognostic models were constructed and externally validated, respectively, in MIBC and NMIBC. Further functional enrichment analyses were also performed to explicate the underlying mechanisms and the differences between the two bladder cancer subtypes.Results: In MIBC, a 7-gene signature for prognostic prediction was constructed. Patients were then divided into high-risk and low-risk groups according to the risk scores calculated by the 7-gene prognostic model. Patients in the high-risk group presented an impaired OS when compared with patients in the low-risk group both in the training cohort and validation cohort. Further functional analyses revealed distinctly different immune statuses between the two risk-stratification groups, speculating that exhausted immune cell function was a cause of the worst OS in the high-risk group. In NMIBC, 6 ferroptosis-related genes were identified that were significantly correlated with recurrence-free survival (RFS). Similarly, a 6-gene prognostic model was constructed and verified as an independent prognostic predictor for RFS. Functional analyses revealed significant differences in the expressions of nuclear division genes between the high-risk group and low-risk group.Conclusion: Two novel ferroptosis-related multigene prognostic models for, respectively, predicting OS in MIBC and RFS in NMIBC were identified in this study, which indicated ferroptosis played vital roles in the oncogenesis and development of MIBC and NMIBC.Keywords: ferroptosis, bladder cancer, MIBC, NMIBC, prognosis, gene signature
format	article
author	Zhang S Wang C Xia W Duan H Qian S Shen H
author_facet	Zhang S Wang C Xia W Duan H Qian S Shen H
author_sort	Zhang S
title	Novel Ferroptosis-Related Multigene Prognostic Models for Patients with Bladder Cancer
title_short	Novel Ferroptosis-Related Multigene Prognostic Models for Patients with Bladder Cancer
title_full	Novel Ferroptosis-Related Multigene Prognostic Models for Patients with Bladder Cancer
title_fullStr	Novel Ferroptosis-Related Multigene Prognostic Models for Patients with Bladder Cancer
title_full_unstemmed	Novel Ferroptosis-Related Multigene Prognostic Models for Patients with Bladder Cancer
title_sort	novel ferroptosis-related multigene prognostic models for patients with bladder cancer
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/8ae1ed9e6e20405691e4f730c8bcc659
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Novel Ferroptosis-Related Multigene Prognostic Models for Patients with Bladder Cancer

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