Functional characterization of the Polε protein family in hepatocellular carcinoma

Abstract Background: Numerous genetic sequencing projects have demonstrated that alterations in Polε (DNA polymerase epsilon ) due to various causes are associated with the development of multiple human cancers. However, the biological functions of its four core genes, POLE1/2/3/4/, in the occurrence, progression, and prognosis of hepatocellular carcinoma(HCC) remain poorly understood to date. Methods: Multi-omics, multi-level deep mining of HCC data from TCGA and other publicly available databases by using online analysis tools from GEPIA2, TIMER2.0, DAVID, Kaplan-Meier plotter, cBioPortal and MethSurv databases, as well asthe R package to assess Polε family members in HCC for their potential biological functions. Results: We found that the four target genes were significantly upregulated in HCC (P<0.001), their high expression was associated with a lower survival rate (P<0.05), and both diagnostic ROC curves and disease-specific survival time-dependent ROC curves suggested that POLE2/3 showed better disease predictive efficacy, and the four genes were significantly associated with immune infiltration, and drug sensitivity analysis suggested that the high expression groups of four target genes showed higher drug sensitivity in some chemotherapeutic drugs(P<0.001). Conclusion: The POLE1/2/3/4are potential prognostic predictive molecules for HCC and correlate with immune infiltration,and high expression of POLE may serve as a potential predictor of the effect of targeted therapies. POLE2/3 may be the potential diagnostic biomarkers for HCC, and the expression level of POLE3 may serve as a biological predictive target for HCC chemotherapy sensitivity.