E2F-mediated POLA2 upregulation is correlated with macrophage infiltration and poor prognosis in hepatocellular carcinoma.

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is the major histological type of primary liver cancer with a relatively poor prognosis, because most HCC cases are usually diagnosed at an advanced stage. Thus, it is essential to explore novel candidate biomarkers for early diagnosis and prognosis predication of HCC. Methods: HCC transcription sequencing data were downloaded and analyzed. POLA2 expression pattern was characterized in tumor development process. POLA2 expression was evaluated by western blotting. Kaplan-Meier plot was utilized to evaluate POLA2's ability for prognosis predication. Correlation analysis and enrichment analysis were performed to explore the functional role of POLA2 in HCC development. Knockdown of E2F1 or E2F4 was used to evaluate their ability in regulating POLA2 expression. CYBERSORT (https//cibersortx.stanford.edu/) was used to estimate the infiltration levels of immune cells. Results: POLA2 was overexpressed in HCC. Moreover, western blotting results showed that POLA2 was upregulated by transcription factors E2F1 rather than E2F4 in HCC. POLA2 facilitated cell cycle progression, DNA replication and DNA repair. High POLA2 expression was correlated with poor overall survival in HCC patients. POLA2 induced macrophage infiltration in the tumor microenvironment by upregulating the expression CSF1 and VEGFA expression. Conclusions: POLA2 is a novel diagnostic and prognostic biomarker of HCC with potential clinical value.