Identification of a 6-gene signature associated with ferroptosis for predicting the prognosis in prostate cancer

Abstract

Ferroptosis is intimately correlated with the development of cancers. We aimed to identify ferroptosis-related prognostic signatures for prognosis prediction of prostate adenocarcinoma (PRAD). The expression profile and clinical data of patients were from The Cancer Genome Atlas Program (TCGA) database. The Cox regression and Lasso analyses were utilized to construct a multigene signature, and the Kaplan-Meier (K-M), receiver operating characteristic (ROC), and decision curve analysis (DCA) curves were used to validate the predictive effect. Additionally, pathway enrichment analyses were performed to explore the potential mechanism associated with biomarkers. In this study, 41 ferroptosis-related genes (FRGs) were differentially expressed between PRAD and normal tissues. Then, we finally constructed a risk model consisting of 6 signatures (Transferrin Receptor (TFRC), Ferritin Heavy Chain 1 (FTH1), Poly (RC) Binding Protein 2 (PCBP2), Acyl-CoA Synthetase Long Chain Family Member 3 (ACSL3), Prion Protein (PRNP), and Lysophosphatidylcholine Acyltransferase 3 (LPCAT3)) among 41 biomarkers. The K-M, ROC, and DCA curves all validated the fine predictive performance of our prognostic signature. We also revealed the significant clinical value of each signature in PRAD. The enrichment analysis suggested the correlation of these genes with the calcium signaling pathway, Transforming Growth Factor Beta 1 (TGF-β), and Wingless-Type MMTV Integration Site Family (WNT) pathways, implying that these genes might be involved in the migration of PRAD. In conclusion, the 6-gene ferroptosis-related signature could serve as a novel biomarker for predicting the prognosis in PRAD. Their function in cancer migration needs further investigation.