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

doi:10.3390/ijms21155508

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

University of Cologne

8 Citations (Scopus)

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 language	English
Article number	5508
Journal	International Journal of Molecular Sciences
Volume	21
Issue number	15
Pages (from-to)	1-14
Number of pages	14
ISSN	1661-6596
DOIs	https://doi.org/10.3390/ijms21155508
Publication status	Published - 31.07.2020

Funding

Funding: This research was funded by grants from the German Cancer Aid to F.O.P. (Deutsche Krebshilfe, grant number 70112676) and L.K. (grant number 70113940), by a junior research fellowship grant of the University of Luebeck to A.O. and a grant of the German Research Foundation (DFG PE1179/9-1) to S.P. J.B. was funded by the German Cancer Aid (Deutsche Krebshilfe) through a Mildred Scheel Nachwuchszentrum Grant (grant number 70113307) and the Else Kröner-Fresenius Stiftung Memorial Grant (2018_EKMS.35).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Centers: University Cancer Center Schleswig-Holstein (UCCSH)

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10.3390/ijms21155508

Cite this

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title = "CDK19 as a potential HPV-independent biomarker for recurrent disease in HNSCC",

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{\textquoteright}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.",

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AU - Paulsen, Finn Ole

AU - Idel, Christian

AU - Ribbat-Idel, Julika

AU - Kuppler, Patrick

AU - Klapper, Luise

AU - Rades, Dirk

AU - Bruchhage, Karl Ludwig

AU - Wollenberg, Barbara

AU - Brägelmann, Johannes

AU - Perner, Sven

AU - Offermann, Anne

PY - 2020/7/31

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N2 - 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.

AB - 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.

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

Abstract

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