Over-expression of RRM2 Predicts Poor Prognosis in Hepatocellular Carcinoma: A Bioinformatics Analysis Based on TCGA Data

Abstract Background: Ribonucleotide reductase regulatory subunit M2 (RRM2) has been reported as an oncogene in some kinds of malignant tumors, such as lung adenocarcinoma, oral squamous cell carcinoma, glioblastoma, and breast cancer. However, there are few studies focus on the clinical significance of RRM2 in Hepatocellular Carcinoma. This work aimed to evaluate the significance of RRM2 in Hepatocellular carcinoma (HCC) based on the Cancer Genome Atlas (TCGA) database.Results: The expression of RRM2 in tumor tissues higher than normal tissues(P＜0.001). The elevated expression of RRM2 in HCC was significantly correlated with T stage(P＜0.05), Pathologic stage(P＜0.05), Tumor status(P＜0.05), Histologic grade(P＜0.001), and AFP(P＜0.001). HCC with higher RRM2 expression was positive associated with worse OS (overall survival), PFS (progression free survival), and DSS (disease specific survival). In the univariate analysis, expression of RRM2, T stage, M stage, Pathologic stage, and Tumor status were negative correlated with OS(P＜0.05). Further analysis by multivariate Cox regression showed that tumor status(P＜0.01) and RRM2 expression(P＜0.05) were independent prognostic factors of OS in HCC. Moreover, GSEA showed that several pathways were enriched in RRM2 high-expression sample, including PD-1 signaling, Cell cycle, P27 pathway, T cell receptor signaling pathway. RRM2 was significantly correlated with the infiltration level of aDC, CD8 T cells, Cytotoxic cells, DC, Mast cells, Neutrophils, NK cells, pDC, T helper cells, T follicular helper cells, Tgd, Th17 cells, and Th2 cells(P＜0.05);Conclusion: The findings from bioinformatic analysis suggest that high expression of RRM2 could be a predictive factor in HCC with poor prognosis. Furthermore, pivotal pathways associated with tumorigenesis are involved in RRM2. Finally, the expression of RRM2 in HCC is related to the level of immune infiltration.