Wise-Draper Trisha, Sendilnathan Arun, Palackdharry Sarah, Pease Nicholas, Qualtieri Julianne, Butler Randall, Sadraei Nooshin Hashemi, Morris John C, Patil Yash, Wilson Keith, Mark Jonathan, Casper Keith, Takiar Vinita, Lane Adam, Privette Vinnedge Lisa
Division of Hematology-Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, 45267.
Division of Hematology-Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, 45267.
Transl Oncol. 2018 Feb;11(1):168-174. doi: 10.1016/j.tranon.2017.12.001. Epub 2017 Dec 28.
Head and neck cancer (HNC) remains the sixth most common malignancy worldwide and survival upon recurrence and/or metastasis remains poor. 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 DEK oncogenic protein, which was previously detected in the urine of patients with bladder cancer and is known to be secreted by immune cells such as macrophages. Here, we investigated if DEK could be detected in human plasma and if DEK levels correlated with clinical and pathological variables of HNSCC. Plasma was separated from the peripheral blood of newly diagnosed, untreated HNSCC patients or age-matched normal healthy controls and analyzed for DEK protein using ELISA. Plasma concentrations of DEK protein were lower in p16-negative tumors compared to both normal controls and patients with p16-positive tumors. Patients with lower plasma concentrations of DEK were also more likely to have late stage tumors and a lower white blood cell count. Contrary to previously published work demonstrating a poor prognosis with high intratumoral DEK levels, we show for the first time that decreased concentrations of DEK in patient plasma correlates with poor prognostic factors, including HPV-negative status as determined by negative p16 expression and advanced tumor stage.
头颈癌（HNC）仍是全球第六大常见恶性肿瘤，复发和/或转移后的生存率仍然很低。传统上，头颈部鳞状细胞癌（HNSCC）与酒精和尼古丁的使用有关，但最近人乳头瘤病毒（HPV）已成为口咽HNSCC的一个有利的预后风险因素。然而，使用额外的生物标志物进行进一步分层以预测患者预后仍然至关重要。一个候选生物标志物是DEK致癌蛋白，该蛋白先前在膀胱癌患者的尿液中被检测到，并且已知由巨噬细胞等免疫细胞分泌。在此，我们研究了是否能在人血浆中检测到DEK，以及DEK水平是否与HNSCC的临床和病理变量相关。从新诊断的、未经治疗的HNSCC患者或年龄匹配的正常健康对照的外周血中分离出血浆，并使用酶联免疫吸附测定（ELISA）分析DEK蛋白。与正常对照和p16阳性肿瘤患者相比，p16阴性肿瘤患者血浆中DEK蛋白浓度较低。血浆中DEK浓度较低的患者也更有可能患有晚期肿瘤和白细胞计数较低。与先前发表的显示肿瘤内DEK水平高预后不良的研究结果相反，我们首次表明患者血浆中DEK浓度降低与不良预后因素相关，包括通过p16阴性表达确定的HPV阴性状态和晚期肿瘤阶段。
