SF3A3 in Liver Hepatocellular Carcinoma: Oncogenic Role and Prognostic Significance
Fangran Liu1, Paul David Blakeley2
1Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong, China.
Introduction:
Splicing factor 3a subunit 3 (SF3A3) is a core component of the SF3A complex essential for pre-mRNA splicing. However, its role and prognostic significance in liver hepatocellular carcinoma (LIHC) remain poorly characterized.
Methods:
We systematically investigated the role of SF3A3 in LIHC using RNA sequencing data, promoter methylation profiles, and proteomic data from The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Associations between SF3A3 expression and clinical or pathological features were analyzed, and the prognostic value of SF3A3 was assessed using survival analysis.
Results:
SF3A3 mRNA and protein levels were elevated in LIHC tumors, whereas promoter methylation was reduced compared with matched normal liver tissues. High SF3A3 expression was positively associated with advanced tumor stage and grade, as well as TP53 mutation status. Elevated SF3A3 expression was linked to significantly poorer overall survival in patients with LIHC. SF3A3 expression showed a positive correlation with tumor-associated fibroblast infiltration. Survival analyses indicated that SF3A3 expression level and tumor stage are key factors associated with LIHC overall survival. Gene set enrichment analysis revealed that tumors with high SF3A3 expression were significantly enriched for pathways related to the GABA-A receptor complex and FGFR3 mutant receptor activity.
Conclusion:
The expression of SF3A3 in LIHC tumors is correlated with adverse pathological features and poor prognosis, and potential biological mechanisms underlying the role of SF3A3 in LIHC were elucidated. This study highlights SF3A3 as a promising biomarker for prognosis and disease severity in LIHC.