1. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
2. Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
3. Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
*Jie-ying Liang and De-shen Wang contributed equally to this work
Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, which makes the prognostic prediction challenging. Ferroptosis, an iron-dependent form of regulated cell death, can be induced by sorafenib. However, the prognostic value of ferroptosis-related genes in HCC remains to be further elucidated. In this study, the mRNA expression profiles and corresponding clinical data of HCC patients were downloaded from public databases. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct a multigene signature in the TCGA cohort. HCC patients from the ICGC cohort were used for validation. Our results showed that most of the ferroptosis-related genes (81.7%) were differentially expressed between HCC and adjacent normal tissues in the TCGA cohort. Twenty-six differentially expressed genes (DEGs) were correlated with overall survival (OS) in the univariate Cox regression analysis (all adjusted P< 0.05). A 10-gene signature was constructed to stratify patients into two risk groups. Patients in the high-risk group showed significantly reduced OS compared with patients in the low-risk group (P < 0.001 in the TCGA cohort and P = 0.001 in the ICGC cohort). The risk score was an independent predictor for OS in multivariate Cox regression analyses (HR> 1, P< 0.01). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Functional analysis revealed that immune-related pathways were enriched, and immune status were different between two risk groups. In conclusion, a novel ferroptosis-related gene signature can be used for prognostic prediction in HCC. Targeting ferroptosis may be a therapeutic alternative for HCC.
Keywords: hepatocellular carcinoma, ferroptosis, gene signature, overall survival, immune status