A Novel Ferroptosis-Related Prognostic Signature Reveals Macrophage Infiltration and EMT Status in Bladder Cancer
Yi‐Lin Yan, Jinming Cai, Zhengnan Huang, Xiangqian Cao, Pengfei Tang, Zeyi Wang, Fang Zhang, Shujie Xia, Bing Shen
Abstract
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.