Universität zu Köln

Becker, Finn, Joerg, Vincent, Hupe, Marie C., Roth, Doris, Krupar, Rosemarie, Lubczyk, Verena, Kuefer, Rainer, Sailer, Verena, Duensing, Stefan, Kirfel, Jutta, Merseburger, Axel S., Braegelmann, Johannes, Perner, Sven and Offermann, Anne (2020). Increased mediator complex subunit CDK19 expression associates with aggressive prostate cancer. Int. J. Cancer, 146 (2). S. 577 - 589. HOBOKEN: WILEY. ISSN 1097-0215

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Abstract

The Mediator complex is a transcriptional regulator interacting with transcription factors and RNA-polymerase-II. Recently, we identified its subunit CDK19 to be specifically expressed in prostate cancer (PCa) and to be functionally implicated in PCa aggressiveness. Aim of our study was to comprehensively characterize the protein expression of CDK19 and its paralog CDK8 in PCa. We performed immunohistochemistry (IHC) for CDK19/CDK8 on a large cohort including needle biopsies from 202 patients, 799 primary tumor foci of radical prostatectomy specimens from 415 patients, 120 locally advanced tumor foci obtained by palliative transurethral resection, 140 lymph node metastases, 67 distant metastases and 82 benigns. Primary tumors were stained for the proliferation marker Ki67, androgen receptor (AR) and ERG. For 376 patients, clinic-pathologic data were available. Primary endpoint was disease-recurrence-free survival (DFS). Nuclear CDK19 and CDK8 expression increases during progression showing the highest intensity in metastatic and castration-resistant tumors. High CDK19 expression on primary tumors correlates with DFS independently from Gleason grade and PSA. Five-year-DFS rates of patients with primary tumors expressing no, moderate and high CDK19 are 73.7, 56.9 and 30.4%, respectively. CDK19 correlates with Gleason grade, T-stage, Ki67 proliferation-index, nuclear AR expression and ERG-status. Therapeutic options for metastatic and castration-resistant PCa remain limited. In the current study, we confirmed an important role of the Mediator subunit CDK19 in advanced PCa supporting current developments to target CDK19 and its paralog CDK8. Furthermore, CDK19 protein expression has the potential to predict disease recurrence independently from established biomarkers thus contributing to individual management for PCa patients.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Becker, Finn UNSPECIFIED UNSPECIFIED UNSPECIFIED Joerg, Vincent UNSPECIFIED UNSPECIFIED UNSPECIFIED Hupe, Marie C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Roth, Doris UNSPECIFIED UNSPECIFIED UNSPECIFIED Krupar, Rosemarie UNSPECIFIED UNSPECIFIED UNSPECIFIED Lubczyk, Verena UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuefer, Rainer UNSPECIFIED UNSPECIFIED UNSPECIFIED Sailer, Verena UNSPECIFIED UNSPECIFIED UNSPECIFIED Duensing, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirfel, Jutta UNSPECIFIED UNSPECIFIED UNSPECIFIED Merseburger, Axel S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Braegelmann, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Perner, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Offermann, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-134896
DOI:	10.1002/ijc.32551
Journal or Publication Title:	Int. J. Cancer
Volume:	146
Number:	2
Page Range:	S. 577 - 589
Date:	2020
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1097-0215
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ERG EXPRESSION; TRANSCRIPTION; POTENT; CELLS; INHIBITION; GENE; IDENTIFICATION; ACTIVATION; GUIDELINES; MUTATIONS Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13489