title: Circulating Epstein-Barr virus-encoded micro-RNAs as potential biomarkers for nasal natural killer/T-cell lymphoma.
abstract: Nasal natural killer/T-cell lymphoma (NNKTL) is an Epstein-Barr virus (EBV)-associated malignancy and is characterized by local invasion and widespread dissemination, with a consequent poor prognosis. Micro-RNAs (miRNAs) play roles in the pathogenesis of several malignancies by regulating gene expression and have been recently identified as stable entities in serum. Here, we investigated the value of circulating EBV-miRNAs as biomarkers for NNKTL. Sera of patients with NNKTL were subjected to miRNA polymerase chain reaction (PCR)-array analysis, after which serum EBV-miRNA levels were verified using quantitative PCR. The latter analysis revealed high miR-BART2-5p, miR-BART7-3p, miR-BART13-3p, and miR-BART1-5p expression levels in sera of patients with NNKTL and indicated accurate values for discriminating patients with NNKTL from healthy controls. Levels of these 4 EBV-miRNAs, which were secreted from NNKTL cells, significantly decreased after treatment compared with those before treatment. Furthermore, a high circulating miR-BART2-5p level was associated with disease progression and poor prognosis in patients with NNKTL. Our findings demonstrate that circulating EBV-miRNAs, particularly miR-BART2-5p, may serve as potential diagnostic and prognostic biomarkers in patients with NNKTL.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Komabayashi
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Kan
authors.initials: K
authors.lastname: Kishibe
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nagato
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Seigo
authors.initials: S
authors.lastname: Ueda
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Takahara
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Harabuchi
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000821:virology*; D055354:Exosomes; D005260:Female; D020869:Gene Expression Profiling; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D054391:Lymphoma, Extranodal NK-T-Cell / Q000097:blood* / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood*; D012372:ROC Curve; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012367:RNA, Viral
keywords: Epstein-Barr virus; circulating micro-RNA; miR-BART2-5p; nasal natural killer/T-cell lymphoma