Citation: | ZHENG Chaoyue, ZHANG Shengxiao, HE Peifeng, YU Qi, CHENG Lingjing, FENG Shuang, KONG Teng, SUN Xiangfei. Identification of differentially expressed genes in dermatomyositis and prediction of therapeutic drugs[J]. Journal of Clinical Medicine in Practice, 2023, 27(15): 86-92. DOI: 10.7619/jcmp.20231190 |
To investigate the possible pathogenesis, potential therapeutic targets and drugs of dermatomyositis (DM).
Chip information was downloaded from the Gene Expression Synthesis (GEO) database for healthy people and DM patients who met screening criteria. Differentially expressed genes (DEGs) were screened using R language related software packages; the gene ontology (GO) functional enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of DEGs were analyzed. The protein interaction network was constructed using STRING online database and Cytoscape software, and key genes were screened and verified. CIBERSORT algorithm was used to analyze the infiltration of immune cells, and the correlation between the expression of hub genes and the abundance of immune cells was analyzed. The DREIMT online analysis tool and Coremine Medical database were used to predict potential drugs to treat DM diseases.
Compared with healthy people, 402 DEGs were up-regulated and 150 DEGs were down-regulated in muscle tissue, 686 DEGs were up-regulated and 284 DEGs were down-regulated in skin tissue, and 170 DEGs were shared between muscle and skin. The results of GO and KEGG enrichment analysis showed that the above DEGs mainly enriched in the innate immune response, defense response to viruses, cytoplasm, plasma membrane and other items, and enriched in the novel coronavirus infection disease, influenza-A, measles, hepatitis C and other pathways. A total of 10 core genes were screened, which were STAT1, MX1, IFIT3, OAS2, IFI35, RSAD2, IFIT1, OAS1, ISG15 and IRF7. Among the 22 kinds of immune cell infiltration, plasma cell infiltration dominated in muscle tissue, while M2 macrophages penetrated in skin tissue in large numbers. Through the analysis of core genes, the top 10 small molecule chemical drugs and 9 traditional Chinese medicines were predicted.
In this study, the hub genes and drugs screened by bioinformatics method may play an important role in the treatment of DM.
[1] |
张雅静, 岳伟. 皮肌炎诊断与治疗进展[J]. 中国现代神经疾病杂志, 2022, 22(6): 533-541. https://www.cnki.com.cn/Article/CJFDTOTAL-XDJB202206015.htm
|
[2] |
SENA P, GIANATTI A, GAMBINI D. Dermatomyositis: clinicopathological correlations[J]. G Ital Dermatol Venereol, 2018, 153(2): 256-264.
|
[3] |
李然, 左婷, 王璐瑶, 等. 肌炎抗体在炎性肌病中的表达及意义[J]. 实用临床医药杂志, 2021, 25(15): 8-13, 17. doi: 10.7619/jcmp.20212570
|
[4] |
TANBOON J, NISHINO I. COVID-19-associated myositis may be dermatomyositis[J]. Muscle Nerve, 2021, 63(1): E9-E10.
|
[5] |
郭巧玲, 赵文鹏, 李葆宸, 等. 皮肌炎/多发性肌炎中巨噬细胞极化偏移与病毒宏基因组学的研究进展[J]. 中华风湿病学杂志, 2021, 25(8): 550-554.
|
[6] |
RAGUSA F. Dermatomyositis and mig[J]. Clin Ter, 2019, 170(2): e142-e147.
|
[7] |
THOMPSON C, PIGUET V, CHOY E. The pathogenesis of dermatomyositis[J]. Br J Dermatol, 2018, 179(6): 1256-1262. doi: 10.1111/bjd.15607
|
[8] |
MATSUDA S, KOTANI T, ISHIDA T, et al. Exploration of pathomechanism using comprehensive analysis of serum cytokines in polymyositis/dermatomyositis-interstitial lung disease[J]. Rheumatology, 2020, 59(2): 310-318. doi: 10.1093/rheumatology/kez301
|
[9] |
ZUO Y B, FENG Q, JIN L C, et al. Regulation of the linear ubiquitination of STAT1 controls antiviral interferon signaling[J]. Nat Commun, 2020, 11(1): 1146. doi: 10.1038/s41467-020-14948-z
|
[10] |
DAM VAN P, DESMECHT D, GARIGLIANY M M, et al. Anti-influenza A virus activities of type Ⅰ/Ⅲ interferons-induced Mx1 GTPases from different mammalian species[J]. J Interferon Cytokine Res, 2019, 39(5): 274-282. doi: 10.1089/jir.2018.0157
|
[11] |
WANG J H, DAI M, CUI Y G, et al. Association of abnormal elevations in IFIT3 with overactive cyclic GMP-AMP synthase/Stimulator of interferon genes signaling in human systemic lupus erythematosus monocytes[J]. Arthritis Rheumatol, 2018, 70(12): 2036-2045. doi: 10.1002/art.40576
|
[12] |
LIU G Q, LEE J H, PARKER Z M, et al. ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity[J]. Nat Microbiol, 2021, 6(4): 467-478. doi: 10.1038/s41564-021-00884-1
|
[13] |
SARKAR S N, BANDYOPADHYAY S, GHOSH A, et al. Enzymatic characteristics of recombinant medium isozyme of 2'-5'oligoadenylate synthetase[J]. J Biol Chem, 1999, 274(3): 1848-1855. doi: 10.1074/jbc.274.3.1848
|
[14] |
MUSUMECI G, CASTROGIOVANNI P, BARBAGALLO I, et al. Expression of the OAS gene family is highly modulated in subjects affected by juvenile dermatomyositis, resembling an immune response to a dsRNA virus infection[J]. Int J Mol Sci, 2018, 19(9): 2786. doi: 10.3390/ijms19092786
|
[15] |
PABLOS J L, SANTIAGO B, GALINDO M, et al. Keratinocyte apoptosis and p53 expression in cutaneous lupus and dermatomyositis[J]. J Pathol, 1999, 188(1): 63-68. doi: 10.1002/(SICI)1096-9896(199905)188:1<63::AID-PATH303>3.0.CO;2-E
|
[16] |
JIAN D, WANG W, ZHOU X, et al. Interferon-induced protein 35 inhibits endothelial cell proliferation, migration and re-endothelialization of injured arteries by inhibiting the nuclear factor-kappa B pathway[J]. Acta Physiol, 2018, 223(3): e13037. doi: 10.1111/apha.13037
|
[17] |
GREENBERG S A, PINKUS J L, PINKUS G S, et al. Interferon-alpha/beta-mediated innate immune mechanisms in dermatomyositis[J]. Ann Neurol, 2005, 57(5): 664-678. doi: 10.1002/ana.20464
|
[18] |
WONG D, KEA B, PESICH R, et al. Interferon and biologic signatures in dermatomyositis skin: specificity and heterogeneity across diseases[J]. PLoS One, 2012, 7(1): e29161. doi: 10.1371/journal.pone.0029161
|
[19] |
YUAN Y K, MIAO Y, QIAN L P, et al. Targeting UBE4A revives viperin protein in epithelium to enhance host antiviral defense[J]. Mol Cell, 2020, 77(4): 734-747. e7. doi: 10.1016/j.molcel.2019.11.003
|
[20] |
WANG L Q, LIU Q, HU X P, et al. Enhanced oral absorption and liver distribution of polymeric nanoparticles through traveling the enterohepatic circulation pathways of bile acid[J]. ACS Appl Mater Interfaces, 2022, 14(37): 41712-41725. doi: 10.1021/acsami.2c10322
|
[21] |
CHOUDHURY S, MOULICK D, BORAH A, et al. In search of drugs to alleviate suppression of the host's innate immune responses against SARS-CoV-2 using a molecular modeling approach[J]. In Silico Pharmacol, 2021, 9(1): 26. doi: 10.1007/s40203-021-00085-y
|
[22] |
SWAIM C D, SCOTT A F, CANADEO L A, et al. Extracellular ISG15 signals cytokine secretion through the LFA-1 integrin receptor[J]. Mol Cell, 2017, 68(3): 581-590, e5. doi: 10.1016/j.molcel.2017.10.003
|
[23] |
SUN W C, SUN Y C, LIN H, et al. Dysregulation of the type Ⅰ interferon system in adult-onset clinically amyopathic dermatomyositis has a potential contribution to the development of interstitial lung disease[J]. Br J Dermatol, 2012, 167(6): 1236-1244. doi: 10.1111/j.1365-2133.2012.11145.x
|
[24] |
CAPPELLETTI C, BAGGI F, ZOLEZZI F, et al. Type Ⅰ interferon and Toll-like receptor expression characterizes inflammatory myopathies[J]. Neurology, 2011, 76(24): 2079-2088. doi: 10.1212/WNL.0b013e31821f440a
|
[25] |
陈皓然, 吴秋惠, 王鸯鸯, 等. 皮肌炎和多发性肌炎相关间质性肺炎的药物治疗[J]. 中南药学, 2020, 18(5): 811-815.
|
[26] |
邓韵珊, 眭道顺. 近30年皮肌炎中医证治用药规律分析[J]. 中医药导报, 2018, 24(3): 42-44. https://www.cnki.com.cn/Article/CJFDTOTAL-HNZB201803012.htm
|