CDK19 as a potential HPV-independent biomarker for recurrent disease in HNSCC

Finn Ole Paulsen, Christian Idel, Julika Ribbat-Idel, Patrick Kuppler, Luise Klapper, Dirk Rades, Karl Ludwig Bruchhage, Barbara Wollenberg, Johannes Brägelmann, Sven Perner*, Anne Offermann

*Corresponding author for this work

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.

Original languageEnglish
Article number5508
JournalInternational Journal of Molecular Sciences
Volume21
Issue number15
Pages (from-to)1-14
Number of pages14
ISSN1661-6596
DOIs
Publication statusPublished - 31.07.2020

Research Areas and Centers

  • Centers: University Cancer Center Schleswig-Holstein (UCCSH)

Fingerprint

Dive into the research topics of 'CDK19 as a potential HPV-independent biomarker for recurrent disease in HNSCC'. Together they form a unique fingerprint.

Cite this