Investigating genetic drivers of dermatomyositis pathogenesis using meta-analysis.
Investigating genetic drivers of dermatomyositis pathogenesis using meta-analysis.
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DOI：
10.1016/j.heliyon.2020.e04866
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发表时间：
2020-09
期刊：
影响因子：
4
通讯作者：
Jarjour W
中科院分区：
文献类型：
--
作者：
Aljabban J;Syed S;Syed S;Rohr M;Weisleder N;McElhanon KE;Hasan L;Safeer L;Hoffman K;Aljabban N;Mukhtar M;Adapa N;Allarakhia Z;Panahiazar M;Neuhaus I;Kim S;Hadley D;Jarjour W
皮肌炎 (DM) 是一种进行性、特发性炎症性肌病，其发病机制尚不清楚。糖尿病的一个标志是患乳腺癌、卵巢癌和肺癌的风险增加。由于抗 TIF-1-γ（三联基序 (TRIM) 蛋白的成员）的自身抗体与恶性肿瘤密切相关，因此我们检测了 TRIM 基因家族的表达，以确定可能导致 DM 发病机制的途径。我们利用 GEO 平台的搜索标签分析资源来搜索 NCBI 基因表达综合库，以阐明 TRIM 家族基因表达以及 DM 病理学中的致癌驱动因素。我们对人类皮肤（60 名糖尿病患者与 34 名健康人）和肌肉（71 名糖尿病患者与 22 名健康人）的数据进行了荟萃分析。我们确定了参与先天免疫、抗原呈递、代谢和其他细胞过程的基因作为 DM 疾病活动的促进剂，并证实了先前关于存在强干扰素特征的观察结果。此外，对 DM 肌肉样本的分析显示 TRIM14、TRIM22、TRIM25、TRIM27 和 TRIM38 上调。同样，对 DM 皮肤样本的分析显示 TRIM5、TRIM6、TRIM 14、TRIM21、TRIM34 和 TRIM38 上调，而 TRIM73 下调。此外，我们注意到癌基因 IGLC1、IFI44、POSTN、MYC、NPM1 和 IDO1 的上调，并将这种变化与干扰素信号传导相关。虽然与分析的遗传数据相关的临床数据不包含有关这些队列中恶性肿瘤的临床数据，但观察到的遗传变化可能与与糖尿病恶性肿瘤风险增加相关的稳态和信号变化有关。我们的结果表明以前未知的基因是 DM 病理学的潜在驱动因素，并表明某些 TRIM 家族成员可能具有疾病特异性作用，具有潜在的诊断和治疗意义。生物信息学、遗传学、免疫学、分子生物学、病理学、皮肌炎、三方家族蛋白、特发性肌病、自身免疫。
Dermatomyositis (DM) is a progressive, idiopathic inflammatory myopathy with poorly understood pathogenesis. A hallmark of DM is an increased risk for developing breast, ovarian, and lung cancer. Since autoantibodies against anti-TIF-1-γ, a member of the tripartite motif (TRIM) proteins, has a strong association with malignancy, we examined expression of the TRIM gene family to identify pathways that may be contributing to DM pathogenesis. We employed the Search Tag Analyze Resource for GEO platform to search the NCBI Gene Expression Omnibus to elucidate TRIM family gene expression as well as oncogenic drivers in DM pathology. We conducted meta-analysis of the data from human skin (60 DM vs 34 healthy) and muscle (71 DM vs 22 healthy). We identified genes involved in innate immunity, antigen presentation, metabolism, and other cellular processes as facilitators of DM disease activity and confirmed previous observations regarding the presence of a robust interferon signature. Moreover, analysis of DM muscle samples revealed upregulation of TRIM14, TRIM22, TRIM25, TRIM27, and TRIM38. Likewise, analysis of DM skin samples showed upregulation of TRIM5, TRIM6, TRIM 14, TRIM21, TRIM34, and TRIM38 and downregulation of TRIM73. Additionally, we noted upregulation of oncogenes IGLC1, IFI44, POSTN, MYC, NPM1, and IDO1 and related this change to interferon signaling. While the clinical data associated with genetic data that was analyzed did not contain clinical data regarding malignancy in these cohorts, the observed genetic changes may be associated with homeostatic and signaling changes that relate to the increased risk in malignancy in DM. Our results implicate previously unknown genes as potential drivers of DM pathology and suggest certain TRIM family members may have disease-specific roles with potential diagnostic and therapeutic implications. Bioinformatics, Genetics, Immunology, Molecular biology, Pathology, Dermatomyositis, Tripartite family proteins, Idiopathic myopathies, Autoimmunity.
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影响因子：
6.7
作者：
Barr SD;Smiley JR;Bushman FD
通讯作者：
Bushman FD
影响因子：
3.7
作者：
Bai X;Zhang E;Ye H;Nandakumar V;Wang Z;Chen L;Tang C;Li J;Li H;Zhang W;Han W;Lou F;Zhang D;Sun H;Dong H;Zhang G;Liu Z;Dong Z;Guo B;Yan H;Yan C;Wang L;Su Z;Li Y;Jones L;Huang XF;Chen SY;Gao J
通讯作者：
Gao J
影响因子：
3.7
作者：
Carthagena L;Bergamaschi A;Luna JM;David A;Uchil PD;Margottin-Goguet F;Mothes W;Hazan U;Transy C;Pancino G;Nisole S
通讯作者：
Nisole S
影响因子：
4.8
作者：
Bergeron, A;D'Astous, M;Tanguay, RM
通讯作者：
Tanguay, RM
影响因子：
20.3
作者：
de Leval, Laurence;Rickman, David S.;Gaulard, Philippe
通讯作者：
Gaulard, Philippe