Ferroptosis-related gene signature predicts prognosis and immunotherapy response in hepatocellular carcinoma: A multi-cohort retrospective study

Hepatocellular carcinoma (HCC), characterized by elevated incidence and mortality rates, has a considerable economic impact worldwide. The function of ferroptosis within the tumor microenvironment of HCC is crucial, and the specific contributions of ferroptosis-related genes (FRGs) are yet to be fully explored. FRG expression levels and relevant clinical data were sourced from The Cancer Genome Atlas. Two distinct ferroptosis-related subtypes were identified in liver cancer and their interrelationships were comprehensively examined. Using Cox regression and least absolute shrinkage and selection operator regression analysis, we created a predictive model based on FRGs to forecast overall survival and assess the potential benefits of immunotherapy in patients with HCC. Quantitative reverse transcription-polymerase chain reaction and IHC assays were conducted on clinical HCC specimens to validate the key FRGs. Significant differences in gene mutations, immune reactions, and prognostic outcomes were observed between the 2 distinct ferroptosis-related subtypes. An eight-gene signature consisting of SLC1A5, KIF20A, SLC7A11, CARS1, MYCN, PRDX6, GPX4, and KLF2 was established as a predictive model for liver cancer and was validated against data from GSE76427 and the International Cancer Genome Consortium cohorts. According to the FRG model, individuals classified as low-risk exhibited more favorable survival prospects compared to their high-risk counterparts (P < .05). Overall, our investigation highlights the promise of FRGs as prognostic biomarkers and immunotherapy response in HCC, providing a novel approach for personalized patient management.