Integrative Multi-Database Bioinformatics Characterization of FANCE in Hepatocellular Carcinoma: Prognostic, Epigenetic, Immune, and ncRNA Associations

Background and Objectives: The Fanconi anemia complementation group E (FANCE) is a protein component of the Fanconi anemia (FA) DNA repair complex and contributes to genome integrity. However, its molecular and clinical relevance in liver hepatocellular carcinoma (LIHC) remains incompletely understood. This study characterized the FANCE expression, prognosis, epigenetics, immune responses, noncoding RNA (ncRNA) networks, and other related molecular processes in LIHC. Materials and Methods: An integrative multi-database bioinformatics analysis was conducted using public databases and web-based platforms. FANCE expression, DNA methylation, co-expression profiles, and functional enrichment; immune cell infiltration; miRNA–ncRNA, chemical–gene, and protein–protein interactions; treatment response; and survival were evaluated. Results: FANCE expression was higher in LIHC than in non-tumor liver tissues, and this was linked to shorter survival duration. Promoter methylation was lower in LIHC, and select CpG sites were related to FANCE expression and survival. Immune analyses identified heterogeneous relationships between FANCE and inferred immune cell populations. hsa-miR-101-3p was reduced in LIHC, negatively correlated with FANCE, and linked to prolonged survival; subsequent network analysis identified candidate lncRNAs, small ncRNAs, circRNA-linked genes, and pseudogenes. FANCE-related transcriptional profiles were enriched in the cell cycle, DNA replication, FA, and other DNA-repair processes, whereas negatively correlated genes were mainly linked to hepatic metabolic functions. Exploratory treatments identified drug-dependent survival patterns related to FANCE expression and elevated levels in responders to specific immune-checkpoint inhibitors, although the discriminatory performance was modest. Conclusions: Increased FANCE expression in LIHC was linked to molecular features involving DNA methylation, immune cell composition, ncRNA-related interactions, and DNA repair programs as well as shorter survival. These findings provide an integrated molecular context for FANCE in LIHC but do not establish a causal regulation or therapeutic predictive value. Independent clinical and experimental validation studies are warranted to determine its biological and clinical significance.