[1]李华水,谢文焌,林强,等.桥本氏甲状腺炎差异基因筛选、分析及潜在治疗药物预测[J].福建医药杂志,2021,43(04):18-22.
点击复制

桥本氏甲状腺炎差异基因筛选、分析及潜在治疗药物预测()
分享到:

《福建医药杂志》[ISSN:1002-2600/CN:35-1071/R]

卷:
43
期数:
2021年04期
页码:
18-22
栏目:
临床研究
出版日期:
2021-08-15

文章信息/Info

文章编号:
1002-2600(2021)04-0018-05
作者:
李华水谢文焌林强陈雨征1程雪飞陈梅琴
福建省立医院基本外科(福州 350001)
关键词:
桥本氏甲状腺炎生物信息学分析差异表达基因免疫反应潜在治疗药物
分类号:
R581.4
文献标志码:
A
摘要:
目的 通过生物信息学技术筛选出桥本氏甲状腺炎(HT)差异表达基因,对差异基因进行分析得出与HT发生及发展密切相关的基因,并通过核心基因预测潜在的HT治疗药物。 方法 采用GEO2R在线工具分析HT数据集GSE6339和 GSE138198,获取HT差异表达基因。通过Webgestalt数据库分析差异表达基因的生物学过程、细胞成分、分子功能及富集的信号通路,通过String数据库构建HT差异表达基因蛋白互作相关作用(PPI)网络,通过Cytosccape软件MCC算法计算出差异基因中的10个核心基因,通过Genemania数据库构建核心基因分子互作网络并通过药物-基因相互作用数据库(DGIdb)预测HT潜在治疗药物。 结果 共筛选出74个HT差异表达基因,其中上调基因67个,下调基因7个,生物学功能和信号通路富集分析显示差异表达基因主要富集于T细胞受体复合物中参与免疫相关信号通路。通过String数据库最终得到具58个节点、342条边的PPI网络,检测发现的核心基因间具有共表达、共定位区域,核心基因主要功能为活化免疫细胞。在药物-基因相互作用数据库中发现了3个潜在治疗药物,分别是希普利珠单抗、阿法赛特、依伐利珠单抗。 结论 HT样本中共有74个差异表达基因;差异表达基因的功能与机体免疫功能相关;核心基因主要功能为活化免疫细胞;希普利珠单抗、阿法赛特、依伐利珠单抗是HT潜在的治疗药物。

参考文献/References:

[1]Sinclair D.Clinical and laboratory aspects of thyroid autoantibodies[J].Ann Clin Biochem,2006,43(Pt 3):173-183.
[2]Zhang Y,Wang H,Pan X,et al.Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a higher risk of miscarriage:A systematic review and meta-analysis[J].PLoS One,2017,12(4):e0175708.
[3]Ferrari S M,Fallahi P,Elia G,et al.Thyroid autoimmune disorders and cancer[J].Semin Cancer Biol,2020,64:135-146.
[4]Winther K H,Papini E,Attanasio R,et al.A 2018 European Thyroid Association Survey on the Use of Selenium Supplementation in Hashimoto's Thyroiditis[J].Eur Thyroid J,2020,9(2):99-105.
[5]Fagerholm S C,MacPherson M,James M J,et al.The CD11b-integrin (ITGAM) and systemic lupus erythematosus[J].Lupus,2013,22(7):657-663.
[6]Hom G,Graham R R,Modrek B,et al.Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX[J].N Engl J Med,2008,358(9):900-909.
[7]Anaya J M,Kim-Howard X,Prahalad S,et al.Evaluation of genetic association between an ITGAM non-synonymous SNP (rs1143679) and multiple autoimmune diseases[J].Autoimmun Rev,2012,11(4):276-280.
[8]Malesiński R,Bakunowicz-tazarczyk A,Wysocka J.The role of chemokines CCL3/MIP-1 alfa and CCL4/MIP-1 beta in pathogenesis of dry eye syndrome[J].Klin Oczna,2008,110(7-9):277-279.
[9]Ferrer-Francesch X,Caro P,Alcalde L,et al.One-tube-PCR technique for CCL2,CCL3,CCL4 and CCL5 applied to fine needle aspiration biopsies shows different profiles in autoimmune and non-autoimmune thyroid disorders[J].J Endocrinol Invest,2006,29(4):342-349.
[10]Rotondi M,Chiovato L.The chemokine system as a therapeutic target in autoimmune thyroid diseases:a focus on the interferon-γ inducible chemokines and their receptor[J].Curr Pharm Des,2011,17(29):3202-3216.
[11]Foucher E D,Blanchard S,Preisser L,et al.IL-34- and M-CSF-induced macrophages switch memory T cells into Th17 cells via membrane IL-1α[J].Eur J Immunol,2015,45(4):1092-1102.
[12]Hutchinson J A,Riquelme P,Sawitzki B,et al.Cutting Edge:Immunological consequences and trafficking of human regulatory macrophages administered to renal transplant recipients[J].J Immunol,2011,187(5):2072-2078.
[13]Wang S,Liu Y,Zhao N,et al.IL-34 Expression Is Reduced in Hashimoto's Thyroiditis and Associated With Thyrocyte Apoptosis[J].Front Endocrinol (Lausanne),2018,9:629.
[14]Burchill M A,Yang J,Vang K B,et al.Interleukin-2 receptor signaling in regulatory T cell development and homeostasis[J].Immunol Lett,2007,114(1):1-8.
[15]Kyrgios I,Fragou A,Kotanidou E P,et al.DNA methylation analysis within the IL2RA gene promoter in youth with autoimmune thyroid disease[J].Eur J Clin Invest,2020,50(3):e13199.
[16]Shao T,Shi W,Zheng J Y,et al.Costimulatory function of Cd58/Cd2 interaction in adaptive humoral immunity in a Zebrafish model[J].Front Immunol,2018,9:1204.
[17]Greaves D R,Gordon S.Macrophage-specific gene expression:current paradigms and future challenges[J].Int J Hematol,2002,76(1):6-15.
[18]Ngoenkam J,Schamel W W,Pongcharoen S.Selected signal-ling proteins recruited to the T-cell receptor-CD3 complex[J].Immunology,2018,153(1):42-50.
[19]Podestà M A,Binder C,Sellberg F,et al.Siplizumab selec-tively depletes effector memory T cells and promotes a relative expansion of alloreactive regulatory T cells in vitro[J].Am J Transplant,2020,20(1):88-100.
[20]Sbidian E,Chaimani A,Garcia-Doval I,et al.Systemic pharmacological treatments for chronic plaque psoriasis:a network meta-analysis[J].Cochrane Database Syst Rev,2017,12(12):CD011535.
[21]Hsu S H,Tsai T F.Evolution of the inclusion/exclusion criteria and primary endpoints in pivotal trials of biologics and small oral molecules for the treatment of psoriasis[J].Expert Rev Clin Pharmacol,2020,13(3):211-232.

备注/Memo

备注/Memo:
1 福建省卫生职业技术学校
第一作者简介:李华水(1983-),男,硕士,副主任医师,主要研究方向为甲状腺相关疾病诊治。Email:170871544@qq.com
通信作者简介:谢文焌(1989-),男,硕士,主治医师,主要研究方向为甲状腺相关疾病诊治。Email:xiewenjun89@163.com
更新日期/Last Update: 2021-08-15