Research Paper Volume 13, Issue 6 pp 8095—8114
Expression and prognostic value of transcription-associated cyclin-dependent kinases in human breast cancer
- 1 Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- 2 Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Received: December 6, 2020 Accepted: January 14, 2021 Published: March 3, 2021
https://doi.org/10.18632/aging.202595How to Cite
Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Abbreviations
CDKs: cyclin-dependent kinases; TA-CDKs: transcription-associated cyclin-dependent kinases; TCGA: The Cancer Genome Atlas; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; BP: biological process; CC: cellular component; MF: molecular function; OS: overall survival; RFS: relapse-free survival; DSS: disease-specific survival; DFS: disease-free survival; PFS: progression-free survival; HER2: human epidermal growth factor receptor 2; ER: estrogen receptor.