Identification of a Novel Ferroptosis-Related Gene Prognostic Signature in Bladder Cancer

Abstract

BackgroundFerroptosis is a newly found non-apoptotic forms of cell death that plays an important role in tumors. However, the prognostic value of ferroptosis-related genes (FRG) in bladder cancer (BLCA) have not been well examined.MethodsFRG data and clinical information were collected from The Cancer Genome Atlas (TCGA). Then, significantly different FRGs were investigated by functional enrichment analyses. The prognostic FRG signature was identified by univariate cox regression and least absolute shrinkage and selection operator (LASSO) analysis, which was validated in TCGA cohort and Gene Expression Omnibus (GEO) cohort. Subsequently, the nomogram integrating risk scores and clinical parameters were established and evaluated. Additionally, Gene Set Enrichment Analyses (GSEA) was performed to explore the potential molecular mechanisms underlying our prognostic FRG signature. Finally, the expression of three key FRGs was verified in clinical specimens.ResultsThirty-two significantly different FRGs were identified from TCGA–BLCA cohort. Enrichment analyses showed that these genes were mainly related to the ferroptosis. Seven genes (TFRC, G6PD, SLC38A1, ZEB1, SCD, SRC, and PRDX6) were then identified to develop a prognostic signature. The Kaplan–Meier analysis confirmed the predictive value of the signature for overall survival (OS) in both TCGA and GEO cohort. A nomogram integrating age and risk scores was established and demonstrated high predictive accuracy, which was validated through calibration curves and receiver operating characteristic (ROC) curve [area under the curve (AUC) = 0.690]. GSEA showed that molecular alteration in the high- or low-risk group was closely associated with ferroptosis. Finally, experimental results confirmed the expression of SCD, SRC, and PRDX6 in BLCA.ConclusionHerein, we identified a novel FRG prognostic signature that maybe involved in BLCA. It showed high values in predicting OS, and targeting these FRGs may be an alternative for BLCA treatment. Further experimental studies are warranted to uncover the mechanisms that these FRGs mediate BLCA progression.

Multi-Omics Analysis of Novel Signature for Immunotherapy Response and Tumor Microenvironment Regulation Patterns in Urothelial Cancer

“…Besides, we used multiple omics data such as genomics, transcriptomics to make the analysis more in-depth and complete. Compared with many previous reported signatures ( Sun et al, 2021a ; Sun et al, 2021b ; He et al, 2021 ; Yan et al, 2021 ), the predictive power of TMsig is more outstanding. Besides, the TMSig scoring system we constructed can effectively assess the immune profile of patients with urothelial cancer and predict patient prognosis, which we have validated with a sample of 1025 cases.…”

A Novel Prognostic Signature Based on Ferroptosis-Related Genes Predicts the Prognosis of Patients With Advanced Bladder Urothelial Carcinoma

“…PRDX6 could inhibit the high oxidative damage caused by ferroptosis and thus promote the proliferation of BLCA ( 25 ). In addition, SCD promotes the proliferation of BLCA via fatty acid metabolic pathway in ferroptosis ( 26 ). In sum, these 8 FRGs may participate in the key biological processes such as proliferation, invasion and metastasis of BLCA through ferroptosis pathway.…”

Identification of Survival and Therapeutic Response-Related Ferroptosis Regulators in Bladder Cancer through Data Mining and Experimental Validation

“…Some articles also construct a signature only to predict the prognosis results of patients [ 25 , 26 ]. In our research, we also predict the effect of immune therapy.…”