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Increased mediator complex subunit CDK19 expression associates with aggressive prostate cancer.

Finn Becker1,2, Vincent Joerg1,2, Marie C Hupe3

  • 1Pathology of the University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.

International Journal of Cancer
|July 5, 2019
PubMed
Summary

High CDK19 expression in prostate cancer (PCa) correlates with increased disease recurrence. This finding supports targeting CDK19 and CDK8 for advanced PCa, potentially improving patient management.

Keywords:
CDK19CDK8Mediator complexbiomarkerprostate cancer

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Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • The Mediator complex regulates gene transcription, interacting with transcription factors and RNA polymerase II.
  • CDK19, a Mediator subunit, is upregulated in prostate cancer (PCa) and linked to its aggressiveness.

Purpose of the Study:

  • To comprehensively characterize the protein expression of CDK19 and its paralog CDK8 in prostate cancer.
  • To evaluate the prognostic value of CDK19 expression in relation to disease recurrence.

Main Methods:

  • Immunohistochemistry (IHC) was used to assess CDK19 and CDK8 protein expression in a large cohort of PCa samples (biopsies, radical prostatectomy, metastases) and benign tissue.
  • Staining for Ki67, androgen receptor (AR), and ERG was performed on primary tumors.
  • Clinic-pathologic data and disease-recurrence-free survival (DFS) were analyzed.

Main Results:

  • Nuclear CDK19 and CDK8 expression increased with tumor progression, peaking in metastatic and castration-resistant PCa.
  • High CDK19 expression in primary tumors independently correlated with shorter DFS, irrespective of Gleason grade and PSA levels.
  • CDK19 expression showed correlations with Gleason grade, T-stage, Ki67 proliferation, nuclear AR expression, and ERG status.

Conclusions:

  • CDK19 plays a significant role in advanced prostate cancer progression.
  • CDK19 protein expression can predict disease recurrence in PCa patients, independent of existing biomarkers.
  • Targeting CDK19 and CDK8 presents a potential therapeutic strategy for advanced and castration-resistant PCa.