Universität zu Köln

Paulsen, Finn-Ole, Idel, Christian, Ribbat-Idel, Julika, Kuppler, Patrick ORCID: 0000-0002-5667-8481, Klapper, Luise, Rades, Dirk, Bruchhage, Karl-Ludwig, Wollenberg, Barbara, Braegelmann, Johannes, Perner, Sven and Offermann, Anne (2020). CDK19 as a Potential HPV-Independent Biomarker for Recurrent Disease in HNSCC. Int. J. Mol. Sci., 21 (15). BASEL: MDPI. ISSN 1422-0067

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Abstract

The Mediator complex is a central integrator of transcription and a hub for the regulation of gene expression. Cyclin dependent kinase (CDK) 19 and its paralog CDK8 are part of its kinase domain and contribute to cancer progression in different cancer entities. STAT1 is an important immune modulator and a downstream substrate of CDK8/CDK19 mediated phosphorylation. So far, little is known about CDK19's role in head and neck squamous cell carcinoma (HNSCC) progression, its link to STAT1 activity, and related immune modulation. Immunohistochemistry for CDK19, activated pSTAT1, and PD-L1, known to be affected by STAT1, was conducted on samples of 130 primary tumors, 71 local recurrences, 32 lymph node metastases, and 25 distant metastases of HNSCC. Compared to primary tumors, CDK19 is overexpressed in local recurrences and distant metastases as well as in primary tumors that developed local recurrence after initial therapy. Patients with high-CDK19-expressing primary tumors have a significantly shorter disease-free survival. CDK19 expression correlates with pSTAT1 expression in primary tumors associated with recurrent disease, local recurrent tumors, lymph node metastases, and distant metastases. pSTAT1 expression correlates with PD-L1 expression in recurrent tumors. Our findings identify CDK19 as a potential biomarker in HNSCC to predict recurrent disease and support recent developments to target CDK19 and its paralog CDK8 in advanced cancer.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Paulsen, Finn-Ole UNSPECIFIED UNSPECIFIED UNSPECIFIED Idel, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Ribbat-Idel, Julika UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuppler, Patrick UNSPECIFIED orcid.org/0000-0002-5667-8481 UNSPECIFIED Klapper, Luise UNSPECIFIED UNSPECIFIED UNSPECIFIED Rades, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruchhage, Karl-Ludwig UNSPECIFIED UNSPECIFIED UNSPECIFIED Wollenberg, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Braegelmann, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Perner, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Offermann, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-324859
DOI:	10.3390/ijms21155508
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	21
Number:	15
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MEDIATOR COMPLEX; ADJUVANT CHEMOTHERAPY; PROTEIN EXPRESSION; NECK-CANCER; HEAD; CELLS; INHIBITION; STAT1; TRANSCRIPTION; INDUCTION Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32485