RAD54L promotes progression of hepatocellular carcinoma via the homologous recombination repair pathway

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence worldwide. The underlying mechanisms remain poorly understood. The DNA metabolic process of homologous recombination repair (HRR) has been linked to a high probability of tumorigenesis and drug resistance. This study aimed to determine the role of HRR in HCC and identify critical HRR-related genes that affect tumorigenesis and prognosis. A total of 613 tumor and 252 para-carcinoma tissue samples were collected from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) to obtain differentially expressed genes (DEGs). HRR-related genes were assessed using gene enrichment and pathway analyses. Survival analysis was performed using the Kaplan-Meier method in the Gene Expression Profiling Interactive Analysis portal. The levels of RAD54L in the HRR pathway were detected by RT-qPCR and western blotting in para-carcinoma and HCC tissues and in L02 normal human liver cells and Huh7 HCC cells. Immunohistochemistry (IHC) was performed on the clinical specimens to determine the connection between gene expression and clinical features. Bioinformatics analysis revealed that the HRR pathway was enriched in HCC tissues. Upregulation of HRR pathway DEGs in HCC tissues was positively correlated with tumor pathological staging and negatively associated with patient overall survival. RAD54B, RAD54L, and EME1 genes in the HRR pathway were screened as markers for predicting HCC prognosis. RT-qPCR identified RAD54L as the most significantly expressed of the three genes. Western blotting and IHC quantitative analyses further demonstrated that RAD54L protein levels were higher in HCC tissues. IHC analysis of 39 pairs of HCC and para-carcinoma tissue samples also revealed an association between RAD54L and Edmondson-Steiner grade and the proliferation-related gene Ki67. The collective findings positively correlate RAD54L in the HRR signaling pathway with HCC staging and implicate RAD54L as a marker to predict HCC progression.