High level of viral microRNA-BART20-5p expression is associated with worse survival of patients with Epstein-Barr virus-associated gastric cancer

// Byung Woog Kang 1, * , YongHun Choi 2, 3, * , Oh Kyoung Kwon 4 , Seung Soo Lee 4 , Ho Young Chung 4 , Wansik Yu 4 , Han Ik Bae 5 , An Na Seo 5 , Hyojeung Kang 6 , Suk Kyeong Lee 7 , Seong Woo Jeon 8 , Keun Hur 2, 3 , Jong Gwang Kim 1 1 Department of Oncology/Hematology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Kyungpook National University Cancer Research Institute, Kyungpook National University, Daegu, South Korea 2 Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, South Korea 3 BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, South Korea 4 Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, South Korea 5 Department of Pathology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, South Korea 6 College of Pharmacy, Institute of Microorganisms and Research Institute of Pharmaceutical Sciences, Kyunpook National University, Daegu, South Korea 7 Department of Medical Lifescience, College of Medicine, Catholic University of Korea, Seoul, South Korea 8 Department of Gastroeneterology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, South Korea * These authors contributed equally to this work Correspondence to: Jong Gwang Kim, email: jkk21c@knu.ac.kr Keun Hur, email: KeunHur@knu.ac.kr Keywords: gastric cancer, epstein-barr virus, microRNA, prognosis, BART Received: August 02, 2016      Accepted: January 10, 2017      Published: January 19, 2017 ABSTRACT This study analyzed the relationship between several Epstein-Barr virus (EBV) microRNA (miRNA) expression profiles and the clinicopathologic features of patients with EBV-associated gastric cancer. The miRNA expression was examined in 59 tumor and 39 paired normal mucosal tissues from available formalin-fixed paraffin embedded tissue samples. The expression levels of miR-BamHI fragment A rightward transcript (BART)1-5p, miR-BART4-5p, and miR-BART20-5p were determined using a quantitative real-time polymerase chain reaction. The expression of all three analyzed EBV microRNAs was significantly higher in the tumor tissue than in the paired normal tissue ( P < 0.001 for each). When the median value of the EBV microRNA expression levels was used as the cutoff point, a high BART20-5p expression was associated with worse recurrence-free survival ( P = 0.034) in a multivariate analysis including age and pathologic stage. In conclusion, the expression level of BART20-5p may predict recurrence-free survival for patients with EBV-associated gastric cancer. Further studies are warranted to clarify the roles of EBV BART microRNAs in the carcinogenesis, and their potential as a biomarker and therapeutic target for EBV-associated gastric cancer.