Minezaki Teruumi, Usui Yoshihiko, Asakage Masaki, Takanashi Masakatsu, Shimizu Hiroyuki, Nezu Naoya, Narimatsu Akitomo, Tsubota Kinya, Umazume Kazuhiko, Yamakawa Naoyuki, Kuroda Masahiko, Goto Hiroshi
Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Department of Molecular Pathology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
J Clin Med. 2020 Jun 12;9(6):1844. doi: 10.3390/jcm9061844.
Vitreoretinal lymphoma (VRL) is a non-Hodgkin lymphoma of the diffuse large B cell type (DLBCL), which is an aggressive cancer causing central nervous system related mortality. The pathogenesis of VRL is largely unknown. The role of microRNAs (miRNAs) has recently acquired remarkable importance in the pathogenesis of many diseases including cancers. Furthermore, miRNAs have shown promise as diagnostic and prognostic markers of cancers. In this study, we aimed to identify differentially expressed miRNAs and pathways in the vitreous and serum of patients with VRL and to investigate the pathogenesis of the disease.
Vitreous and serum samples were obtained from 14 patients with VRL and from controls comprising 40 patients with uveitis, 12 with macular hole, 14 with epiretinal membrane, 12 healthy individuals. The expression levels of 2565 miRNAs in serum and vitreous samples were analyzed.
Expression of the miRNAs correlated significantly with the extracellular matrix (ECM) ‒receptor interaction pathway in VRL. Analyses showed that miR-326 was a key driver of B-cell proliferation, and miR-6513-3p could discriminate VRL from uveitis. MiR-1236-3p correlated with vitreous interleukin (IL)-10 concentrations. Machine learning analysis identified miR-361-3p expression as a discriminator between VRL and uveitis.
Our findings demonstrate that aberrant microRNA expression in VRL may affect the expression of genes in a variety of cancer-related pathways. The altered serum miRNAs may discriminate VRL from uveitis, and serum miR-6513-3p has the potential to serve as an auxiliary tool for the diagnosis of VRL.
玻璃体视网膜淋巴瘤（VRL）是一种弥漫性大B细胞型非霍奇金淋巴瘤（DLBCL），是一种侵袭性癌症，可导致中枢神经系统相关死亡。VRL的发病机制在很大程度上尚不清楚。微小RNA（miRNA）在包括癌症在内的许多疾病的发病机制中最近已变得极为重要。此外，miRNA已显示出作为癌症诊断和预后标志物的前景。在本研究中，我们旨在鉴定VRL患者玻璃体和血清中差异表达的miRNA及其相关通路，并研究该疾病的发病机制。
从14例VRL患者以及包括40例葡萄膜炎患者、12例黄斑裂孔患者、14例视网膜前膜患者和12例健康个体的对照组中获取玻璃体和血清样本。分析血清和玻璃体样本中2565种miRNA的表达水平。
VRL中miRNA的表达与细胞外基质（ECM）-受体相互作用通路显著相关。分析表明，miR-326是B细胞增殖的关键驱动因子，miR-6513-3p可区分VRL和葡萄膜炎。miR-1236-3p与玻璃体白细胞介素（IL）-10浓度相关。机器学习分析确定miR-361-3p的表达可区分VRL和葡萄膜炎。
我们的研究结果表明，VRL中异常的微小RNA表达可能影响多种癌症相关通路中基因的表达。血清中改变的miRNA可区分VRL和葡萄膜炎，血清miR-6513-3p有潜力作为VRL诊断的辅助工具。
