Xi Jianying, Wang Liang, Yan Chong, Song Jie, Song Yang, Chen Ji, Zhu Yongjun, Chen Zhiming, Jin Chun, Ding Jianyong, Zhao Chongbo
Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
J Thorac Dis. 2019 Jun;11(6):2315-2323. doi: 10.21037/jtd.2019.06.01.
Myasthenia gravis (MG) is a group of autoimmune disease which could be accompanied by thymoma. Many differences have been observed between thymoma-associated MG (TAMG) and non-MG thymoma (NMG). However, the molecular difference between them remained unknown. This study aimed to explore the differentially expressed genes (DEGs) between the two categories and to elucidate the possible pathogenesis of TAMG further.
DEGs were calculated using the RNA-Sequencing data from 11 TAMG and 10 NMG in The Cancer Genome Atlas (TCGA) database. GeneAnalytics was performed to characterize the associations between DEGs and tissues and cells, diseases, gene ontology (GO) terms, pathways, phenotypes, and drug/compounds, respectively. Genes related to T cells were sorted out using LifeMapDiscovery Cells and Tissues Database. Genes directly related to the phenotype of autoimmune diseases that were identified by VarElect were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
The expression level of 169 genes showed a significant difference between the two groups, with 94 up-regulated and 75 down-regulated. Overexpression of six genes (, , , , , ), which are expressed in T cells and directly related to autoimmune disease through VarElect, was identified. The overexpression of soluble BTLA (sBTLA) (P=0.027), CCR7 (P=0.0018), TNFRSF25 (P=0.0013) and ANKRD55 (P=0.0026) was validated by RT-qPCR in thymoma tissues from our center.
Overexpression of sBTLA, CCR7, TNFRSF25 and ANKRD55 was identified and validated by RT-qPCR, which could partly explain the underlying pathogenesis in TAMG.
重症肌无力（MG）是一组可伴有胸腺瘤的自身免疫性疾病。胸腺oma相关MG（TAMG）和非MG胸腺瘤（NMG）之间已观察到许多差异。然而，它们之间的分子差异仍然未知。本研究旨在探讨这两类之间的差异表达基因（DEG），并进一步阐明TAMG的可能发病机制。
使用来自癌症基因组图谱（TCGA）数据库中11例TAMG和10例NMG的RNA测序数据计算DEG。分别进行基因分析以表征DEG与组织和细胞、疾病、基因本体（GO）术语、途径、表型以及药物/化合物之间的关联。使用LifeMapDiscovery细胞和组织数据库筛选与T细胞相关的基因。通过VarElect鉴定的与自身免疫性疾病表型直接相关的基因通过逆转录定量聚合酶链反应（RT-qPCR）进行验证。
两组之间169个基因的表达水平存在显著差异，其中94个上调，75个下调。鉴定出六个在T细胞中表达并通过VarElect与自身免疫性疾病直接相关的基因（、、、、、）的过表达。通过RT-qPCR在我们中心的胸腺瘤组织中验证了可溶性BTLA（sBTLA）（P=0.027）、CCR7（P=0.0018）、TNFRSF25（P=0.0013）和ANKRD55（P=0.0026）的过表达。
通过RT-qPCR鉴定并验证了sBTLA、CCR7、TNFRSF25和ANKRD55的过表达，这可能部分解释了TAMG的潜在发病机制。
