CDK19 as a Potential HPV-Independent Biomarker for Recurrent Disease in HNSCC
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CDK19 as a Potential HPV-Independent Biomarker for Recurrent Disease in HNSCC. / Paulsen, Finn-Ole; Idel, Christian; Ribbat-Idel, Julika; Kuppler, Patrick; Klapper, Luise; Rades, Dirk; Bruchhage, Karl-Ludwig; Wollenberg, Barbara; Brägelmann, Johannes; Perner, Sven; Offermann, Anne.
In: INT J MOL SCI, Vol. 21, No. 15, 5508, 31.07.2020.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - CDK19 as a Potential HPV-Independent Biomarker for Recurrent Disease in HNSCC
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
Y1 - 2020/7/31
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.
KW - Biomarkers, Tumor/genetics
KW - Cyclin-Dependent Kinases/genetics
KW - Disease Progression
KW - Disease-Free Survival
KW - Female
KW - Humans
KW - Kaplan-Meier Estimate
KW - Lymphatic Metastasis/genetics
KW - Male
KW - Mediator Complex/genetics
KW - Neoplasm Recurrence, Local/genetics
KW - Papillomaviridae/genetics
KW - Papillomavirus Infections/genetics
KW - Phosphorylation
KW - Progression-Free Survival
KW - Squamous Cell Carcinoma of Head and Neck/genetics
U2 - 10.3390/ijms21155508
DO - 10.3390/ijms21155508
M3 - SCORING: Journal article
C2 - 32752128
VL - 21
JO - INT J MOL SCI
JF - INT J MOL SCI
SN - 1661-6596
IS - 15
M1 - 5508
ER -