Downregulated Ferroptosis-Related Gene STEAP3 as a Novel Diagnostic and Prognostic Target for Hepatocellular Carcinoma and Its Roles in Immune Regulation

Abstract

Ferroptosis, a distinct type of regulated cell death, has been reported to be involved in the tumorigenesis of liver hepatocellular carcinoma (LIHC). However, the precise functions and potential mechanisms of ferroptosis in LIHC were still poorly understood. Herein, we investigated the biological roles of ferroptosis-related gene STEAP3 in LIHC. STEAP3 was previously proved to serve a key regulator in ferroptosis via mediating the iron metabolism. Comprehensive bioinformatics from several databases revealed that STEAP3 was significantly downregulated in LIHC tissues and exhibited the favorable prognostic significance in LIHC patients. The downregulated STEAP3 was further confirmed in two LIHC cells Huh7 and MHCC97H using real-time PCR and western blot. And STEAP3 overexpression significantly inhibited the cell proliferation in Huh7 and MHCC97H cells. In addition, clinical data identified the relationship between STEAP3 expression and several clinicopathological parameters of LIHC patients, including histologic grade, alpha fetal protein (AFP) concentration, etc. Receiver operation characteristic (ROC) curve revealed STEAP3 as a potential diagnostic biomarker for LIHC patients. Moreover, the co-expression network of STEAP3 was explored to gain a better insight into its underlying signaling pathways. Finally, aberrant STEAP3 might participate in varieties of immune-associated signatures in LIHC pathogenesis, including immunostimulators, immunoinhibitors, chemokines, and chemokine receptors. Taken together, these findings could enhance our knowledge regarding the inhibitory roles and underlying biological significance of STEAP3 in LIHC tumorigenesis.