Expression of CDK7 correlates with molecular subtypes and predicts clinical outcomes in breast cancer

BACKGROUND: Cyclin-dependent kinase 7 (CDK7) belongs to CDK family, which is involved in transcriptional activity and cell cycle progression. Recent studies have suggested that CDK7 inhibitor is effective in the treatment of breast cancer, whereas, the efficacy of antitumor response varies significantly in different subtypes of breast cancer. However, the underlying connection between CDK7 and molecular subtypes of breast cancer is currently unknown. METHODS: To further elucidate the role of CDK7 in breast cancer, we investigated the association of CDK7 expression with different molecular subtypes and clinical outcomes in breast cancer using the Oncomine, GENT2, UALCAN and PrognoScan database. The correlation between CDK7 mRNA expression and promoter methylation was established using MEXPRESS datasets. And the CDK7 expression with different stages and subtypes was also examined by immunohistochemistry (IHC) assay in 140 breast cancer patients. RESULTS: We found that the expression of CDK7 was increased in breast cancer. Besides, our data demonstrated that both CDK7 hypomethylation status and copy number variations (CNVs) were highly correlated with mRNA overexpression. Moreover, based on the tissue array of 140 patients and more than 4,000 samples from bc-GenExMiner database, CDK7 protein levels were significantly higher in luminal and human epidermal growth factor receptor 2 positive (HER2+) breast cancer in comparison with triple-negative breast cancer (TNBC) subtype. The expression of CDK7 was prominently correlated with molecular markers of different subtypes of breast cancer. Furthermore, the results of the univariate analysis indicated that high CDK7 expression was dramatically associated with poor overall survival (OS) (P=0.0323, HR =2.08). CONCLUSIONS: Our results highlighted that elevated CDK7 expression was correlated with molecular subtypes and acted as a candidate biomarker of poor prognosis in breast cancer.