A Novel Ferroptosis-Related Prognostic Signature Reveals Macrophage Infiltration and EMT Status in Bladder Cancer
Bladder cancer (BC) belongs to one of the most common and highly heterogeneous malignancies. Ferroptosis is a newly discovered regulated cell death (RCD), characterized by accumulation of toxic lipid peroxides, and plays a crucial role in tumor progression. Here, we conducted a comprehensive analysi...
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doaj-91232ed7a2ff4ca196cb8df68745e2a12021-08-20T08:27:21ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-08-01910.3389/fcell.2021.712230712230A Novel Ferroptosis-Related Prognostic Signature Reveals Macrophage Infiltration and EMT Status in Bladder CancerYilin Yan0Jinming Cai1Zhengnan Huang2Xiangqian Cao3Pengfei Tang4Zeyi Wang5Fang Zhang6Shujie Xia7Shujie Xia8Bing Shen9Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai, ChinaDepartment of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaInstitute of Urology, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBladder cancer (BC) belongs to one of the most common and highly heterogeneous malignancies. Ferroptosis is a newly discovered regulated cell death (RCD), characterized by accumulation of toxic lipid peroxides, and plays a crucial role in tumor progression. Here, we conducted a comprehensive analysis on the transcriptomics data of ferroptosis-related genes in BC based on The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets. In our study, a 6-gene signature was identified based on the potential prognostic ferroptotic regulatory genes. Furthermore, our signature revealed a good independent prognostic ability in BC. Patients with low-risk score exhibited higher FGFR3 mutation rates while high risk score had a positive association with higher RB1 mutation rates. Meanwhile, higher proportions of macrophages were observed in high BC risk group simultaneously with four methods. Unexpectedly, the risk score showed a significant positive correlation with epithelial-mesenchymal transition (EMT) status. Functional assays indicated that CRYAB and SQLE knockdown was associated with attenuated invasion capacity. Our study revealed a ferroptosis-related risk model for predicting prognostic and BC progression. Our results indicate that targeting ferroptosis may be a therapeutic strategy for BC.https://www.frontiersin.org/articles/10.3389/fcell.2021.712230/fullbladder cancerferroptosisprognostic signaturemacrophageEMT status |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yilin Yan Jinming Cai Zhengnan Huang Xiangqian Cao Pengfei Tang Zeyi Wang Fang Zhang Shujie Xia Shujie Xia Bing Shen |
spellingShingle |
Yilin Yan Jinming Cai Zhengnan Huang Xiangqian Cao Pengfei Tang Zeyi Wang Fang Zhang Shujie Xia Shujie Xia Bing Shen A Novel Ferroptosis-Related Prognostic Signature Reveals Macrophage Infiltration and EMT Status in Bladder Cancer Frontiers in Cell and Developmental Biology bladder cancer ferroptosis prognostic signature macrophage EMT status |
author_facet |
Yilin Yan Jinming Cai Zhengnan Huang Xiangqian Cao Pengfei Tang Zeyi Wang Fang Zhang Shujie Xia Shujie Xia Bing Shen |
author_sort |
Yilin Yan |
title |
A Novel Ferroptosis-Related Prognostic Signature Reveals Macrophage Infiltration and EMT Status in Bladder Cancer |
title_short |
A Novel Ferroptosis-Related Prognostic Signature Reveals Macrophage Infiltration and EMT Status in Bladder Cancer |
title_full |
A Novel Ferroptosis-Related Prognostic Signature Reveals Macrophage Infiltration and EMT Status in Bladder Cancer |
title_fullStr |
A Novel Ferroptosis-Related Prognostic Signature Reveals Macrophage Infiltration and EMT Status in Bladder Cancer |
title_full_unstemmed |
A Novel Ferroptosis-Related Prognostic Signature Reveals Macrophage Infiltration and EMT Status in Bladder Cancer |
title_sort |
novel ferroptosis-related prognostic signature reveals macrophage infiltration and emt status in bladder cancer |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-08-01 |
description |
Bladder cancer (BC) belongs to one of the most common and highly heterogeneous malignancies. Ferroptosis is a newly discovered regulated cell death (RCD), characterized by accumulation of toxic lipid peroxides, and plays a crucial role in tumor progression. Here, we conducted a comprehensive analysis on the transcriptomics data of ferroptosis-related genes in BC based on The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets. In our study, a 6-gene signature was identified based on the potential prognostic ferroptotic regulatory genes. Furthermore, our signature revealed a good independent prognostic ability in BC. Patients with low-risk score exhibited higher FGFR3 mutation rates while high risk score had a positive association with higher RB1 mutation rates. Meanwhile, higher proportions of macrophages were observed in high BC risk group simultaneously with four methods. Unexpectedly, the risk score showed a significant positive correlation with epithelial-mesenchymal transition (EMT) status. Functional assays indicated that CRYAB and SQLE knockdown was associated with attenuated invasion capacity. Our study revealed a ferroptosis-related risk model for predicting prognostic and BC progression. Our results indicate that targeting ferroptosis may be a therapeutic strategy for BC. |
topic |
bladder cancer ferroptosis prognostic signature macrophage EMT status |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.712230/full |
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