Nezu Naoya, Usui Yoshihiko, Asakage Masaki, Shimizu Hiroyuki, Tsubota Kinya, Narimatsu Akitomo, Umazume Kazuhiko, Yamakawa Naoyuki, Ohno Shin-Ichiro, Takanashi Masakatsu, Kuroda Masahiko, Goto Hiroshi
Department of Ophthalmology, Tokyo Medical University, Tokyo 160-0023, Japan.
Department of Molecular Pathology, Tokyo Medical University, Tokyo 160-8402, Japan.
J Clin Med. 2020 Aug 5;9(8):2530. doi: 10.3390/jcm9082530.
The molecular pathogenesis of orbital lymphoproliferative disorders, such as immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and orbital mucosa-associated lymphoid tissue (MALT) lymphoma, remains essentially unknown. Differentiation between the two disorders, which is important since the work-up and treatment can vary greatly, is often challenging due to the lack of specific biomarkers. Although miRNAs play an important role in the regulation of carcinogenesis and inflammation, the relationship between miRNA and orbital lymphoproliferative diseases remains unknown. We performed a comprehensive analysis of 2565 miRNAs from biopsy and serum specimens of 17 cases with IgG4-ROD, where 21 cases with orbital MALT lymphoma were performed. We identified specific miRNA signatures and their miRNA target pathways, as well as the network analysis for IgG4-ROD and orbital MALT lymphoma. Machine-learning analysis identified miR-202-3p and miR-7112-3p as the best discriminators of IgG4-ROD and orbital MALT lymphoma, respectively. Enrichment analyses of biological pathways showed that the longevity-regulating pathway in IgG4-ROD and the mitogen-activated protein kinase (MAPK) signaling pathway in orbital MALT lymphoma was most enriched by target genes of downregulated miRNAs. This is the first evidence of miRNA profiles of biopsy and serum specimens of patients with IgG4-ROD and orbital MALT lymphoma. These data will be useful for developing diagnostic and therapeutic interventions, as well as elucidating the pathogenesis of these disorders.
眼眶淋巴增殖性疾病的分子发病机制，如免疫球蛋白G4相关性眼病（IgG4-ROD）和眼眶黏膜相关淋巴组织（MALT）淋巴瘤，基本上仍不清楚。这两种疾病的鉴别很重要，因为检查和治疗方法可能有很大差异，但由于缺乏特异性生物标志物，鉴别往往具有挑战性。尽管微小RNA（miRNA）在癌症发生和炎症调节中起重要作用，但miRNA与眼眶淋巴增殖性疾病之间的关系仍不清楚。我们对17例IgG4-ROD活检和血清标本中的2565种miRNA进行了全面分析，同时对21例眼眶MALT淋巴瘤也进行了分析。我们确定了特异性miRNA特征及其miRNA靶标途径，以及针对IgG4-ROD和眼眶MALT淋巴瘤的网络分析。机器学习分析分别确定miR-202-3p和miR-7112-3p为IgG4-ROD和眼眶MALT淋巴瘤的最佳鉴别指标。生物途径富集分析表明，IgG4-ROD中长寿调节途径和眼眶MALT淋巴瘤中丝裂原活化蛋白激酶（MAPK）信号通路被下调miRNA的靶基因高度富集。这是IgG4-ROD和眼眶MALT淋巴瘤患者活检和血清标本miRNA谱的首个证据。这些数据将有助于开发诊断和治疗干预措施，以及阐明这些疾病的发病机制。
