Background: Head and neck squamous cell carcinoma (HNSCC) has traditionally been associated with alcohol and nicotine use, but more recently the Human Papilloma Virus (HPV) has emerged as a favorable prognostic risk factor for oropharyngeal HNSCC. However, further stratification with additional biomarkers to predict patient outcome continues to be essential. One candidate biomarker is the chromatin remodeling DEK protein, which is both an auto-antigen in autoimmune diseases and an oncogene in epithelial tissues. DEK is secreted by stimulated macrophages and neutrophils and was previously detected in the urine of patients with bladder cancer. Previously, we have reported that DEK mRNA and protein is upregulated in HNC tumor tissue and higher DEK levels are associated with poor prognoses in many types of solid tumors. We hypothesized that DEK could be detected in the plasma of HNC patients, either due to secretion from the tumor or as part of the antitumor immune response, and therefore may be a biomarker for disease status.
Methods: We recruited 38 newly diagnosed HNSCC patients and 37 age-matched normal healthy controls into the study. Plasma isolated from peripheral blood was subjected to DEK specific ELISA and DEK concentration levels were compared to levels found in normal controls, and to clinical and pathological variables.
Results: We show for the first time that DEK can be detected in human plasma. We did not find an association between DEK plasma concentrations and variables including sex, age, race, or drinking/smoking status. However, we detected decreased concentrations of DEK in HNC patients with p16-negative disease and in patients with larger tumor sizes, indicating an association between DEK levels and known prognostic markers. In addition, HNC patients with lower DEK concentrations had a decreased white blood cell count, largely due to differences in lymphocyte and eosinophil counts. This direct association between plasma DEK levels and white blood cell count was independent of p16 status.
Conclusions: Together, the data suggest that lower levels of DEK in HNC patient plasma may be predictive of poor outcome. This is in direct contrast to what is observed with intratumoral levels of DEK protein, in which higher levels of DEK expression are an independent factor predicting poor prognosis. Future studies will investigate the role that secreted DEK, such as that found in the plasma, may have in the antitumor immune response.
Citation Format: Trisha Wise-Draper, Arun Sendilnathan, Sarah Palackdharry, Nicholas Pease, Julianne Qualtieri, Randy Butler, Nooshin Hashemi Sadraei, John C. Morris, Yash Patil, Keith Wilson, Jonathan Mark, Keith Casper, Vinita Takiar, Adam Lane, Lisa M. Privette Vinnedge. Plasma concentrations of the DEK oncogene correlate with pathological variables in a case-control study of patients with HNSCC [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 50.