Komabayashi Yuki, Kishibe Kan, Nagato Toshihiro, Ueda Seigo, Takahara Miki, Harabuchi Yasuaki
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
Hematol Oncol. 2017 Dec;35(4):655-663. doi: 10.1002/hon.2360. Epub 2016 Oct 6.
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.
鼻型自然杀伤/T细胞淋巴瘤（NNKTL）是一种与爱泼斯坦-巴尔病毒（EBV）相关的恶性肿瘤，其特征为局部侵袭和广泛播散，预后较差。微小RNA（miRNA）通过调节基因表达在多种恶性肿瘤的发病机制中发挥作用，并且最近已被确定为血清中的稳定物质。在此，我们研究了循环EBV-miRNA作为NNKTL生物标志物的价值。对NNKTL患者的血清进行miRNA聚合酶链反应（PCR）阵列分析，之后使用定量PCR验证血清EBV-miRNA水平。后一项分析显示，NNKTL患者血清中miR-BART2-5p、miR-BART7-3p、miR-BART13-3p和miR-BART1-5p表达水平较高，并且表明这些指标在区分NNKTL患者与健康对照方面具有准确的价值。这4种从NNKTL细胞分泌的EBV-miRNA水平在治疗后与治疗前相比显著降低。此外，循环miR-BART2-5p水平较高与NNKTL患者的疾病进展和预后不良相关。我们的研究结果表明，循环EBV-miRNA，尤其是miR-BART2-5p，可能作为NNKTL患者潜在的诊断和预后生物标志物。
