Expression and prognostic value of transcription-associated cyclin-dependent kinases in human breast cancer

Aging (Albany NY). 2021 Mar 3;13(6):8095-8114. doi: 10.18632/aging.202595. Epub 2021 Mar 3.

Abstract

The expression and prognostic significance of transcription-associated cyclin-dependent kinases (TA-CDKs) in breast cancer have not been systematically investigated. Using Oncomine, GEPIA2, the Human Protein Atlas, the Kaplan-Meier Plotter, cBioPortal, Metascape, and DAVID 6.8, we profiled the expression of TA-CDKs in breast cancer, inferred their biological functions, and assessed their effect on prognosis. The expression of CDK7/10/13/19 mRNAs in breast cancer tissues was significantly higher than in normal breast tissues. Survival analysis of breast cancer patients revealed that increased CDK8 expression was associated with inferior overall survival (OS), higher expression of CDK7 or CDK8 was associated with inferior relapse-free survival (RFS), but higher expression of CDK13 was associated with favorable RFS and OS. In addition, a high genetic alteration rate (56%) in TA-CDKs was associated with shorter OS. On functional enrichment analysis, top GO enrichment items for TA-CDKs and their neighboring genes included cyclin-dependent protein serine/threonine kinase activity and transferase complex. The top KEGG pathways included cell cycle and mismatch repair. These results suggest that CDK7/8/13 are potential prognostic biomarkers for breast cancer patients and provide novel insight for future studies examining their usefulness as therapeutic targets.

Keywords: CDK; bioinformatics analysis; biomarker; breast cancer; transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / enzymology*
  • CDC2 Protein Kinase / metabolism*
  • Cyclin-Dependent Kinase 8 / metabolism*
  • Cyclin-Dependent Kinase-Activating Kinase
  • Cyclin-Dependent Kinases / metabolism*
  • Disease-Free Survival
  • Female
  • Humans
  • Prognosis

Substances

  • Biomarkers, Tumor
  • CDC2 Protein Kinase
  • CDK13 protein, human
  • CDK8 protein, human
  • Cyclin-Dependent Kinase 8
  • Cyclin-Dependent Kinases
  • Cyclin-Dependent Kinase-Activating Kinase
  • CDK7 protein, human