Identification of a ferroptosis related genes signature and GDF15 contributing to a new perspective for the diagnosis of CRPC.

Prostate cancer (PCa) is a highly prevalent malignancy among men. Castration-resistant prostate cancer (CRPC) is the main pathological type leading to the death of patients. Due to the lack of effective early diagnostic biomarkers, the treatment of CRPC is often lagging. Ferroptosis is a new discovered pathway of cell death. The diagnostic value of ferroptosis-related genes for CRPC is still uncertain. In this study, we identified 10 differently expressed FRGs between 145 hormone-sensitive PCa (HSPC) and 49 CRPC. A novel ferroptosis-related genes (FRGs) signature was constructed using seven FRGs (ABCC5, ACSL1, AKR1C3, CAMKK2, GDF15, PDSS2, and ZFP36), which could distinguish CRPC from HSPC with area under the ROC curve (AUC) = 0.93. This result was confirmed in an independent validation cohort with AUC = 0.90, F1 score = 0.85. Among the seven FRGs, GDF15 independently predicted CRPC with the good performance (AUC = 0.84). Moreover, GDF15 could effectively distinguish PCa from normal tissues (AUC = 0.79 and 0.83 in two cohorts). Two distinct ferroptosis profiles were discovered, and FRGs signature and GDF15 could also effectively distinguish them. GDF15 expression level shows an inverted U-shape with disease progression (normal, HSPC, CRPC). Although GDF15 expression was decreased in CRPC cells, overexpression of GDF15 still facilitates CRPC cells migration and invasion in vitro. Our findings suggest that this novel FRGs signature and GDF15 could be robust biomarkers for predicting CRPC in clinical practice.