Identification of high protein kinase CK2α in HPV(+) oropharyngeal squamous cell carcinoma and correlation with clinical outcomes

Janeen H Trembley, Bin Li, Betsy J Kren, Justin C Peltola, Juan C Manivel, Devi Meyyappan, Amy A Gravely, Mark Klein, Khalil Ahmed, Emiro E Caicedo-Granados

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Oropharyngeal squamous cell carcinoma (OPSCC) incidence is rising worldwide, especially human papillomavirus (HPV)-associated disease. Historically, high levels of protein kinase CK2 were linked with poor outcomes in head and neck squamous cell carcinoma (HNSCC), without consideration of HPV status. This retrospective study examined tumor CK2α protein expression levels and related clinical outcomes in a cohort of Veteran OPSCC patient tumors which were determined to be predominantly HPV(+). Methods. Patients at the Minneapolis VA Health Care System with newly diagnosed primary OPSCC from January 2005 to December 2015 were identified. A total of 119 OPSCC patient tumors were stained for CK2α, p16 and Ki-67 proteins and E6/E7 RNA. CK2α protein levels in tumors and correlations with HPV status and Ki-67 index were assessed. Overall survival (OS) analysis was performed stratified by CK2α protein score and separately by HPV status, followed by Cox regression controlling for smoking status. To strengthen the limited HPV(-) data, survival analysis for HPV(-) HNSCC patients in the publicly available The Cancer Genome Atlas (TCGA) PanCancer RNA- seq dataset was determined for CSNK2A1. Results. The patients in the study population were all male and had a predominant history of tobacco and alcohol use. This cohort comprised 84 HPV(+) and 35 HPV(-) tumors. CK2α levels were higher in HPV(+) tumors compared to HPV(-) tumors. Higher CK2α scores positively correlated with higher Ki-67 index. OS improved with increasing CK2α score and separately OS was significantly better for those with HPV(+) as opposed to HPV(-) OPSCC. Both remained significant after controlling for smoking status. High CSNK2A1 mRNA levels from TCGA data associated with worse patient survival in HPV(-) HNSCC. Conclusions. High CK2α protein levels are detected in HPV(+) OPSCC tumors and demonstrate an unexpected association with improved survival in a strongly HPV(+) OPSCC cohort. Worse survival outcomes for high CSNK2A1 mRNA levels in HPV(-) HNSCC are consistent with historical data. Given these surprising findings and the rising incidence of HPV(+) OPSCC, further study is needed to understand the biological roles of CK2 in HPV(+) and HPV(-) HNSCC and the potential utility for therapeutic targeting of CK2 in these two disease states.

Original languageEnglish (US)
Article numbere12519
JournalPeerJ
Volume9
DOIs
StatePublished - 2021

Bibliographical note

Funding Information:
This work was supported by Merit Review research funds I01 BX003282 and I01 BX005091 awarded by the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service (Khalil Ahmed); Lion’s award (Bin Li); private donation (Emiro Caicedo-Granados). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2021 PeerJ Inc.. All rights reserved.

Keywords

  • Casein kinase II
  • CK2
  • Head and neck neoplasms
  • Human papillomavirus
  • Ki-67
  • Oropharyngeal squamous cell carcinoma
  • Veteran

PubMed: MeSH publication types

  • Journal Article

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