CD73 is associated with poor prognosis in HNSCC

Abstract

// Zhen-Hu Ren 1, 2, * , Cheng-Zhong Lin 1, 2, * , Wei Cao 1, 2 , Rong Yang 1, 2 , Wei Lu 1, 2 , Zhe-Qi Liu 1, 2 , Yi-Ming Chen 1, 2 , Xi Yang 1, 2 , Zhen Tian 3 , Li-Zhen Wang 3 , Jiang Li 3 , Xu Wang 1, 2 , Wan-Tao Chen 1, 2 , Tong Ji 1, 2 , Chen-Ping Zhang 1, 2 1 Department of Oral Maxillofacial-Head and Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China 2 Shanghai Research Institute of Stomatology and Shanghai Key Laboratory of Stomatology, Shanghai 200011, China 3 Department of Oral Pathology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China * These authors contributed equally to this work Correspondence to: Chen-Ping Zhang, email: zhangcp9th@hotmail.com Tong Ji, email: jitong70@hotmail.com Keywords: CD73, adenosine receptor, EGFR, EMT, head and neck squamous cell carcinoma Received: April 18, 2016      Accepted: July 28, 2016      Published: August 20, 2016 ABSTRACT CD73 is a cell surface immunosuppressive enzyme involved in tumor progression and metastasis. While patients whose cancer cells express elevated CD73 are typically associated with an unfavorable outcome, the clinical impact of CD73 expression in patients with Head and neck squamous cell carcinoma (HNSCC) remains unclear. In the present study, we investigated the prognostic significance of CD73 in HNSCC using gene and protein expression analyses. Our results demonstrate that high levels of CD73 are significantly associated with reduced overall survival in patients with HNSCC. We also investigated the functional role of CD73 in vitro and demonstrated that CD73 promotes HNSCC migration and invasion through adenosine A3R stimulation and the activation of EGF/EGFR signaling. Moreover, in vivo xenograft studies demonstrated that CD73 promotes tumorigenesis. In conclusion, our study highlights a role for CD73 as a poor prognostic marker of patient survival and also as a candidate therapeutic target in HNSCCs.