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Updated: Sep 24, 2025

miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
Targeting cyclin-dependent kinase 7-association between CDK7 and pMED1 expression in prostate cancer tissue
Finn-Ole Paulsen1,2, Duan Kang1, Finn Becker1
1Institute of Pathology, University Medical Center Schleswig-Holstein, SH 23562, Luebeck, Germany.
Abstract:
Cyclin-dependent kinase (CDK) 7-mediated phosphorylation of Mediator-complex subunit 1 (MED1) enhances androgen receptor (AR) activity in prostate cancer (PCa). Hyperactive AR-signalling plays a key role for the development of castration resistance. Several CDK7 inhibitors are currently under investigation in Phase I/II trials addressing solid tumours, including PCa. Aim of this study was to characterize the CDK7/phospho-(p)MED1 axis in human tissue. Immunohistochemistry was performed on 595 PCa samples including 394 primary tumour foci obtained by radical prostatectomy (RP), 64 advanced or recurrent tumours obtained by palliative transurethral resection of the prostate (pTUR), 65 lymph node metastases (LNM), 35 distant metastases (DM) and 36 benign samples. CDK7 is expressed in 79.3% of PCa tissues and protein levels are significantly higher in LNM, pTUR and DM and lower in benign tissues compared to primary tumours. CDK7 and pMED1 expression show strong positive correlation. High expression of CDK7 associated with shorter 5-year biochemical recurrence-free-survival (63.0% vs. 85.0%) and reduced survival persists when adjusted for T-Stage, nodal status, resection boundaries, grade group and pre-operative prostate-specific antigen in multivariate Cox-regression (hazard ratio 4.30; 95% CI, 1.43 to 12,40, P = 0.007). High CDK7 and pMED1 levels correlate with nuclear AR expression. CDK7 positive tumours harbour higher Ki67 expression indices and show more frequently positive ERG (ETS-related gene)-status. In conclusion, CDK7 is frequently expressed in human PCa and predicts disease recurrence after RP. Therapeutical inhibition of CDK7 might be a promising approach in treatment of advanced PCa.
Insights
Cyclin-dependent kinase 7 (CDK7) is frequently found in prostate cancer (PCa) and predicts recurrence. Targeting CDK7 may offer a new treatment for advanced PCa.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Androgen receptor (AR) signaling is crucial in prostate cancer (PCa) development and castration resistance.
- Cyclin-dependent kinase (CDK) 7-mediated phosphorylation of Mediator-complex subunit 1 (MED1) enhances AR activity.
- CDK7 inhibitors are under investigation for solid tumors, including PCa.
Purpose of the Study:
- To characterize the CDK7/phospho-MED1 (pMED1) axis in human prostate cancer tissues.
- To evaluate the prognostic significance of CDK7 expression in PCa.
- To explore the correlation between CDK7, pMED1, and AR expression in PCa.
Main Methods:
- Immunohistochemistry was performed on 595 PCa samples, including primary tumors, advanced/recurrent tumors, lymph node metastases (LNM), distant metastases (DM), and benign tissues.
- Protein levels of CDK7 and pMED1 were analyzed.
- Statistical analyses, including multivariate Cox-regression, were used to assess correlations and survival outcomes.
Main Results:
- CDK7 was expressed in 79.3% of PCa tissues, with higher levels in LNM, advanced/recurrent tumors, and DM compared to primary tumors.
- CDK7 and pMED1 expression showed a strong positive correlation.
- High CDK7 expression was significantly associated with shorter 5-year biochemical recurrence-free survival and reduced overall survival, independent of other prognostic factors.
- High CDK7 and pMED1 levels correlated with nuclear AR expression, higher Ki67 indices, and more frequent ETS-related gene (ERG)-positive status.
Conclusions:
- CDK7 is frequently expressed in human PCa and serves as a significant predictor of disease recurrence after radical prostatectomy (RP).
- The CDK7/pMED1 axis is closely linked to AR activity and tumor aggressiveness.
- Therapeutic inhibition of CDK7 presents a promising strategy for treating advanced prostate cancer.
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