Cell cycle kinases (AUKA, CDK1, PLK1) are prognostic biomarkers and correlated with tumor-infiltrating leukocytes in HBV related HCC

J Biomol Struct Dyn. 2023;41(21):11845-11861. doi: 10.1080/07391102.2022.2164056. Epub 2023 Jan 12.

Abstract

Hepatocellular carcinoma (HCC) is one of the high incidence cancers and third leading cause of cancer-related mortality. HBV is the top most risk factor accounting for 50-80% of the HCC cases. Kinases: Aurora kinase A (AURKA), cyclin-dependent kinase (CDK1) and Polo-like kinase 1 (PLK1), the key regulators of cell mitosis are overexpressed in varieties of cancers including HCC. However, the exact role of these genes in prognosis of HCC is not fully unveiled. In addition, there is no such an accurate prognostic biomarker for HBV-related HCC. To address this issue, we performed a multidimensional analysis of AURKA, CDK1 and PLK1 with a series of publicly available databases in multiple cancers and with experimental validation in HBV-related HCC tissues. Overexpression of AURKA, CDK1 and PLK1 was found in multiple cancers including HCC. Elevated expression of these genes could result from lowered DNA methylation and genomic alterations. Transcriptional overexpression was significantly correlated with poor prognosis of HCC patients. The expression levels were also significantly positively associated with tumor grades and stages. Furthermore, the expression levels of these genes had a strong correlation with infiltration of immune cells. Our analysis shows that AURKA, CDK1 and PLK1 are correlated with immune infiltration and are the prognostic biomarkers for HBV-induced HCC.Communicated by Ramaswamy H. Sarma.

Keywords: Hepatocellular carcinoma; bio-informatics; biomarkers; hepatitis B virus; immune infiltration.

MeSH terms

  • Aurora Kinase A / genetics
  • Biomarkers
  • Biomarkers, Tumor / genetics
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Carcinoma, Hepatocellular* / genetics
  • Cell Cycle
  • Cyclin-Dependent Kinases
  • Hepatitis B virus / genetics
  • Hepatitis B virus / metabolism
  • Humans
  • Leukocytes
  • Liver Neoplasms* / genetics
  • Polo-Like Kinase 1
  • Prognosis

Substances

  • Aurora Kinase A
  • Cyclin-Dependent Kinases
  • Biomarkers
  • Biomarkers, Tumor
  • CDK1 protein, human
  • CDC2 Protein Kinase