TOP2A Serves as a Prognostic Marker Associated with Immune Infiltration in Hepatocellular Carcinoma

Abstract Background TOP2A is a key enzyme that controls the topological state of DNA during DNA replication and transcription. We aim to explore the role of TOP2A in hepatocellular carcinoma (HCC). Methods The expression and prognostic value of TOP2A in HCC were analyzed by TIMER, TCGA, GEO, HPA, GEPIA and Kaplan-Meier plotter databases. The potential molecular mechanism of TOP2A in HCC was researched by GSEA software. The construction of the TOP2A gene co-expression network was completed by the cBioPortal database. The relationship between TOP2A and immune cell infiltration in HCC was explored through the CIBERSORT and TIMER databases. Results TOP2A was overexpressed in HCC and was associated with a poor prognosis. High expression of TOP2A was associated with worse pathological grade, deeper invasion depth, and advanced TNM stage, which was an independent unfavorable prognostic factor for HCC (HR = 1.863, P = 0.004). The GSEA results indicated that TOP2A was closely related to tumorigenesis and cellular metabolism. Furthermore, TOP2A and its co-expressed genes were positively associated with tumor-infiltrating immune cells. These co-expressed genes were independent prognostic factors, and the expression of these genes combined with macrophage levels helped to predict prognosis of HCC. In terms of immune infiltration, HCC patients with high TOP2A expression that the proportions of resting memory CD4 + T cells, activated CD4 + T cells, follicular helper T cells, regulatory T cells, macrophages, and neutrophils were significantly increased. The copy number variations of TOP2A affected the level of tumor-infiltrating immune cells. The expression of TOP2A was positively correlated with immune gene markers of T cell exhaustion in the HCC microenvironment. Conclusion TOP2A is a prognostic molecular marker of HCC, which is related to immune cell infiltration.