RAD54L Is a Prognostic Biomarker and Demonstrate Correlation With Drug Sensitivity in Hepatocellular Carcinoma.

Abstract

Hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality, is characterized by its aggressive nature and poor prognosis. This study investigates the role of RAD54L, a protein implicated in homologous recombination repair of DNA double-strand breaks, in the progression of HCC and its potential as a prognostic marker. Expression levels of RAD54L were assessed using transcriptomic data from The Cancer Genome Atlas and Gene Expression Omnibus databases. Kaplan-Meier survival curves and multivariate Cox regression analyses were conducted to evaluate the prognostic significance of RAD54L expression. Furthermore, the study explored immune infiltration, protein-protein interaction (PPI) networks, and functional enrichment analyses to elucidate the underlying mechanisms of RAD54L in HCC pathogenesis. Drug sensitivity was measured in the HepG2 cell line and GDSC database. Results showed that RAD54L was significantly upregulated at the mRNA level in HCC tissues (n = 369) compared to adjacent normal liver samples (n = 50), with high expression correlating with a poorer overall survival and disease-free interval. Functional enrichment analysis demonstrated that ATPase activity, helicase activity, and coenzyme binding pathways might be involved in RAD54L's effects on HCC pathogenesis. Additionally, knockdown of RAD54L in HepG2 cells resulted in reduced proliferation and increased sensitivity to gemcitabine treatment. In conclusion, higher expression of RAD54L is associated with poor prognosis in HCC and may enhance gemcitabine efficacy, suggesting its potential as both a prognostic biomarker and a therapeutic target in HCC management.