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胸腺瘤中免疫相关枢纽基因的鉴定:CD247缺陷与副肿瘤综合征特征

Identification of Immune-Related Hub Genes in Thymoma: Defects in CD247 and Characteristics of Paraneoplastic Syndrome.

作者信息

Deng Lin-Fang

机构信息

College of Sciences, Shanghai University, Shanghai, China.

College of Medicine, Shanghai University, Shanghai, China.

出版信息

Front Genet. 2022 Jun 14;13:895587. doi: 10.3389/fgene.2022.895587. eCollection 2022.

Abstract

Thymomas (Ts) and thymic carcinomas (TCs) are rare primary tumors of the mediastinum. Paraneoplastic syndrome (PNS) is an important feature of thymoma, which presents great challenges to clinicians. The present study uses the weighted gene co-expression network analysis (WGCNA) to identify possible immunologic mechanisms of thymoma. RNA sequencing data from thymoma samples were downloaded from the TCGA. Core genes were taken from the module that is closely related to the WHO's stage of classification. Enhanced analysis using the online database "Metascape" and an overall survival (OS) analysis were carried out via the Kaplan-Meier method. The hub genes were obtained from the protein-protein interaction (PPI) network. In addition, we jointly analyzed multiple sets of PNS data related to thymomas from other sources to verify the correlation between thymomas and PNS. The impact of hub genes on the prognosis of PNS was evaluated via the ROC curve, with simultaneous analysis of immune infiltration by CIBERSORT. The 14 immune hub genes closely related to thymomas were found to be jointly involved in the T-cell receptor signaling pathway. Compared to the normal thymus and type B1/B2 thymoma, there is a lower number of T-cells in type A/B3 thymoma and thymic carcinoma. The expression of genes related to the T-cell receptor signaling pathway appeared defective. The low expression of CD247 and the decrease in the number of mature T-cells are common features among thymomas, specific pulmonary fibrosis, rheumatoid arthritis, and systemic lupus erythematosus.

摘要

胸腺瘤(Ts)和胸腺癌(TCs)是罕见的纵隔原发性肿瘤。副肿瘤综合征(PNS)是胸腺瘤的一个重要特征,给临床医生带来了巨大挑战。本研究使用加权基因共表达网络分析(WGCNA)来确定胸腺瘤可能的免疫机制。胸腺瘤样本的RNA测序数据从TCGA下载。核心基因取自与世界卫生组织分类阶段密切相关的模块。使用在线数据库“Metascape”进行增强分析,并通过Kaplan-Meier方法进行总生存期(OS)分析。中心基因从蛋白质-蛋白质相互作用(PPI)网络中获得。此外,我们联合分析了来自其他来源的多组与胸腺瘤相关的PNS数据,以验证胸腺瘤与PNS之间的相关性。通过ROC曲线评估中心基因对PNS预后的影响,同时用CIBERSORT分析免疫浸润情况。发现与胸腺瘤密切相关的14个免疫中心基因共同参与T细胞受体信号通路。与正常胸腺和B1/B2型胸腺瘤相比,A/B3型胸腺瘤和胸腺癌中的T细胞数量较少。与T细胞受体信号通路相关的基因表达出现缺陷。CD247的低表达和成熟T细胞数量的减少是胸腺瘤、特发性肺纤维化、类风湿关节炎和系统性红斑狼疮的共同特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff4c/9237438/8dda5ca8091d/fgene-13-895587-g001.jpg

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