Topoisomeraseα Gene as a Marker for Prognostic Prediction of Hepatocellular Carcinoma: A Bioinformatics Analysis

Chin Med Sci J. 2022 Dec 31;37(4):331-339. doi: 10.24920/004006.

Abstract

Objective To investigate the expression of topoisomeraseα (TOP2α) in hepatocellular carcinoma (HCC) and its role in predicting prognosis of HCC patients. Methods We used HCC-related datasets in UALCAN, HCCDB, and cBioPortal databases to analyze the expression and mutation of TOP2α and its co-expressed genes in HCC tissues. GO function and KEGG pathway enrichment of TOP2α and its co-expressed genes were identified. The TIMER database was used to analyze infiltration levels of immune cells in HCC. The impacts of TOP2α and its co-expression genes and the infiltrated immune cells on the survival of HCC patients were assayed by Kaplan-Meier plotter analysis. Results TOP2α and its co-expression genes were highly expressed in HCC (P< 0.001) and detrimental to overall survival of HCC patients (P< 0.001). TOP2α and its co-expression genes were mainly involved in cell mitosis and proliferation, and cell cycle pathway (ID: hsa04110, P = 0.001945). TOP2α and its co-expression genes were mutated in HCC and the mutations were significantly detrimental to overall survival (P = 0.0247) and disease-free survival (P = 0.0265) of HCC patients. High TOP2α expression was positively correlated with the infiltration of B cell (r = 0.459, P< 0.01), CD8+ T cell (r = 0.312, P< 0.01), CD4+ T cell (r = 0.370, P< 0.01), macrophage (r = 0.459, P< 0.01), neutrophil (r = 0.405, P< 0.01), and dendritic cell (r = 0.473, P< 0.01) in HCC. The CD8+ T cell infiltration significantly prolonged the 3- and 5-year survival of HCC patients (all P< 0.05), and CD4+ T cell infiltration significantly shortened the 3-, 5-, and 10-year survival of HCC patients (all P< 0.05). ConclusionTOP2α may be an oncogene, which was associated with poor prognosis of HCC patients and could be used as a biomarker for the prognostic prediction of HCC.

Keywords: bioinformatics analysis; disease-free survival; hepatocellular carcinoma; overall survival; topoisomeraseⅡα.

MeSH terms

  • Biomarkers, Tumor / genetics
  • CD8-Positive T-Lymphocytes
  • Carcinoma, Hepatocellular* / diagnosis
  • Carcinoma, Hepatocellular* / genetics
  • Computational Biology
  • DNA Topoisomerases, Type II* / genetics
  • Humans
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / genetics
  • Prognosis

Substances

  • Biomarkers, Tumor
  • TOP2A protein, human
  • DNA Topoisomerases, Type II