Role of ferroptosis-related molecular patterns in hepatocellular carcinoma microenvironment.

Heterogeneity and complexity of hepatocellular carcinoma (HCC) have been an impediment to effective diagnosis and treatment of HCC. Mounting evidence suggests that ferroptosis-related genes (FRGs) regulate the development of HCC by affecting the tumor microenvironment (TME). Herein, we explored the role of ferroptosis-related molecular patterns in the HCC microenvironment. The transcriptome and corresponding clinicopathological data of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, respectively. Molecular patterns of ferroptosis were explored using consensus clustering analysis and ferroptosis-related molecular patterns in the individual patients were analyzed using principal component analysis (PCA). The ability of ferroptosis-related patterns to predict the biological status and survival outcomes of HCC patients was investigated. Based on the expression of FRGs, three molecular patterns related to ferroptosis were identified. Single sample gene set enrichment analysis (ssGSEA) showed that the molecular patterns associated with the worst prognosis were significantly correlated with high infiltration of immunosuppressive cells in the TME. Besides, we identified three ferroptosis gene clusters underlying the different biological features of the three ferroptosis patterns. Patients in the high-risk group had a worse biological status and survival outcomes than those in the low-risk group. This study demonstrates that ferroptosis-related molecular patterns lead to high heterogeneity in HCC. These molecular patterns can be used to assess the survival of HCC patients and guide the design of immunotherapy strategies for HCC patients.