DSCC1 as a Novel Biomarker in Hepatocellular Carcinoma: Diagnostic Potential, Prognostic Impact, Correlation With Key Pathways, and Association With the Immune Landscape.

[BACKGROUND] DSCC1, a key subunit of the alternative RFC complex, is essential for DNA replication and genome stability. While its role in cancers like breast cancer is documented, its function in LIHC remains largely unexplored. This study comprehensively examines DSCC1's involvement in LIHC.

[METHODS] DSCC1 expression in tumor versus normal at the mRNA and protein levels was assessed using UALCAN, GEPIA, OncoDB, HPA, and TIMER databases. Prognostic significance was evaluated via Kaplan-Meier Plotter, PrognoScan, and validated through UALCAN, cBioPortal, TIMER, HPA, and TISIDB. Genomic alterations were analyzed across TCGA cohorts using cBioPortal. Drug sensitivity data were retrieved from GDSC, and pathway activities were explored to elucidate DSCC1's functional impact. Immune cell infiltration and modulatory interactions were examined using TIMER and TISIDB. Functional roles and interaction networks were assessed using GeneMANIA (PPI), SRplot (GO/KEGG), and Spearman correlation. Associations with key oncogenic pathways including cell cycle, EMT, DNA replication, lipogenesis, and glycolysis were explored via cBioPortal.

[RESULTS] DSCC1 was significantly overexpressed at both mRNA and protein levels in LIHC across various stages, grades, lymph node statuses, and molecular subtypes. High DSCC1 expression was consistently associated with poor overall survival. Genomic analysis revealed frequent alterations, with amplification observed in up to 31% of LIHC patients. Pathway activity profiling showed strong activation of the cell cycle, apoptosis, and EMT pathways, alongside suppression of RAS/MAPK and RTK signaling. DSCC1 expression positively correlated with immune infiltration, including CD4/CD8 T cells, macrophages, neutrophils, dendritic cells, and various immune modulators. Functional enrichment and coexpression analyses revealed involvement in DNA replication, chromosome segregation, and mitotic spindle assembly, suggesting a role in promoting genomic instability. DSCC1 was implicated in metabolism, metastasis, and immune-related pathways. Additionally, DSCC1 expression correlated with resistance to drugs such as 17-AAG and Trametinib, and increased sensitivity to PI-103 and Vorinostat.

[CONCLUSION] Overall, this study suggests that DSCC1 may function as a valuable prognostic biomarker, an early diagnostic indicator, and a potential therapeutic target in LIHC, given its diverse involvement in tumor progression, drug responsiveness, immune regulation, and genomic instability.