Subsite-specific association of DEAD box RNA helicase DDX60 with the development and prognosis of oral squamous cell carcinoma

// Ting-Ying Fu 1, 2, * , Chao-Nan Wu 3, 4, * , Huei-Cin Sie 1 , Jiin-Tsuey Cheng 5 , Yaoh-Shiang Lin 6 , Huei-Han Liou 7 , Yu-Kai Tseng 8, 9 , Chih-Wen Shu 7 , Kuo-Wang Tsai 7, 10 , Leing-Ming Yen 1 , Hui-Wen Tseng 11, 12 , Ching-Jiunn Tseng 7, 13, 14, 15 , Luo-Ping Ger 7, 16 , Pei-Feng Liu 7, 17 1 Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 2 Department of Optometry, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan 3 Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 4 Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan 5 Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 6 Department of Otorhinolaryngology-Head & Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 7 Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 8 Department of Orthopedics, Show Chwan Memorial Hospital, Changhua, Taiwan 9 Department of Orthopedics, National Cheng Kung University Hospital, Tainan, Taiwan 10 Department of Chemical Biology, National Pingtung University of Education, Pingtung, Taiwan 11 Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 12 Department of Nursing, Meiho University, Pingtung, Taiwan 13 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan 14 Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan 15 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 16 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 17 Department of Biotechnology, Fooyin University, Kaohsiung, Taiwan * These authors have contributed equally to this work Correspondence to: Luo-Ping Ger, email: lpger@vghks.gov.tw Pei-Feng Liu, email: pfliu@vghks.gov.tw Keywords: DDX60, oral cancer, subsite-specific, tumorigenesis, prognosis Received: April 14, 2016 Accepted: October 28, 2016 Published: November 08, 2016 ABSTRACT The clinical significance and biological function of DEXD/H box helicase 60 (DDX60) in oral cancer remains unknown. Herein, we evaluated the association of DDX60 expression with tumorigenesis and the prognosis of oral squamous cell carcinoma (OSCC). DDX60 expression was examined by immunohistochemistry on tissue microarray slides of 494 OSCC patients, including 180 buccal mucosal SCC (BMSCC), 241 tongue SCC (TSCC), and 73 lip SCC (LSCC) patients. DDX60 expression was significantly increased in all three subsites of OSCC compared to its expression in tumor adjacent normal tissues. However, its association with tumorigenesis was specific to the oral cavity subsite after the stratification of betel quid chewing, smoking, and drinking. Among OSCC patients, higher levels of DDX60 expression were associated with the male gender, a well-differentiated tumor, advanced stage of disease, and a large tumor size with subsite specific features. LSCC patients with high DDX60 expression levels showed shorter disease-specific survival, particularly those with moderately or poorly differentiated tumors. Additionally, TSCC or OSCC patients with high DDX60 expression showed a poor disease-free survival (DFS), particularly those with moderately or poorly differentiated tumors. Therefore, DDX60 is a novel and unfavorable biomarker for tumorigenesis and prognosis of OSCC in a subsite-specific manner.