[1]朱玉珍,吴紫薇,高贻宙,等.特应性皮炎生物标志物鉴定及其免疫浸润研究[J].浙江科技大学学报,2023,(06):475-483.[doi:10.3969/j.issn.1671-8798.2023.06.003 ]
　ZHU Yuzhen,WU Ziwei,GAO Yizhou,et al.Identification of biomarkers in atopic dermatitis and study of its immune infiltration[J].,2023,(06):475-483.[doi:10.3969/j.issn.1671-8798.2023.06.003 ]
点击复制

特应性皮炎生物标志物鉴定及其免疫浸润研究(/HTML)
分享到：

《浙江科技大学学报》[ISSN:2097-5236/CN:33-1431/Z]

卷:
期数:
2023年06期
页码:
475-483
栏目:
出版日期:
2024-01-01

文章信息/Info

Title:
Identification of biomarkers in atopic dermatitis and study of its immune infiltration
文章编号:
1671-8798(2023)06-0475-09
作者:
朱玉珍1; 吴紫薇1; 高贻宙1; UlfMeyer-Hoffert2; 吴志宏1; 2
(1.浙江科技学院 生物与化学工程学院,杭州 310023; 2.德国基尔大学 医学院皮肤学研究所,德国 基尔 24105)
Author(s):
ZHU Yuzhen1;  WU Ziwei1;  GAO Yizhou1;  Ulf Meyer-Hoffert2;  WU Zhihong1; 2
(1.School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, Zhejiang, China; 2.Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany)
关键词:
特应性皮炎;  生物信息学;  机器学习;  免疫浸润;  生物标志物
分类号:
R758.2
DOI:
10.3969/j.issn.1671-8798.2023.06.003
文献标志码:
A
摘要:
【目的】探索与特应性皮炎(atopic dermatitis,AD)相关的生物标志物,并分析免疫细胞浸润在该疾病中的病理作用。【方法】首先从基因表达综合数据库(Gene Expression Omnibus,GEO)下载与AD相关的转录组测序数据,并利用RStudio软件对数据集进行差异表达分析; 其次通过最小绝对收缩和选择算子回归分析(least absolute shrinkage and selection operator,LASSO)、支持向量机递归特征消除特征选择(support vector machine-recursive feature elimination,SVM-RFE)和随机森林(random forest,RF)3种机器学习算法,综合筛查与AD相关的生物标志物; 再次构建受试者工作特征(receiver operating characteristic,ROC)曲线,评估潜在生物标志物的预测价值; 最后通过估计RNA转录本的相对亚群(cell-type identification by estimating relative subsets of RNA transcripts,CIBERSORT)进行细胞类型识别,评估特应性皮炎的免疫细胞浸润情况,并分析潜在生物标志物与免疫浸润细胞之间的相关性。【结果】确定了2个与AD相关的生物标志物,即基质金属肽酶12(matrix metalloproteinase 12,MMP12)和WNT抑制因子1(WNT inhibitory factor 1,WIF1),并且通过ROC曲线说明了这两个基因的诊断价值较高; AD的发病机制与静息肥大细胞、滤泡辅助性T细胞、记忆CD4+T细胞、初始CD4+T细胞、树突状细胞、活化自然杀伤细胞、记忆B细胞及巨噬细胞相关。【结论】本研究结果为特应性皮炎的靶向治疗提供了新思路。

参考文献/References:

[1] SROKA-TOMASZEWSKA J, TRZECIAK M. Molecular mechanisms of atopic dermatitis pathogenesis[J].International Journal of Molecular Sciences,2021,22(8):4130.
[2] PELLEFIGUES C. IgE autoreactivity in atopic dermatitis:paving the road for autoimmune diseases[J].Antibodies(Basel),2020,9(3):47.
[3] 周杰,陈曙光,宋志强.特异性免疫疗法治疗特应性皮炎[J].中华临床免疫和变态反应杂志,2021,15(1):76.
[4] YANG G, SEOK J K, KANG H C, et al. Skin barrier abnormalities and immune dysfunction in atopic dermatitis[J].International Journal of Molecular Sciences,2020,21(8):2867.
[5] CZARNOWICKI T, ESAKI H, GONZALEZ J, et al. Alterations in B-cell subsets in pediatric patients with early atopic dermatitis[J].The Journal of Allergy and Clinical Immunology,2017,140(1):134.
[6] MÖBUS L, RODRIGUEZ E, HARDER I, et al. Elevated NK-cell transcriptional signature and dysbalance of resting and activated NK cells in atopic dermatitis[J].The Journal of Allergy and Clinical Immunology,2021,147(5):1959.
[7] KASRAIE S, WERFEL T. Role of macrophages in the pathogenesis of atopic dermatitis[J].Mediators Inflamm,2013,2013(2):942375.
[8] 杨雷,伍搏宇,熊辉,等.基于基因芯片技术结合CIBERSORT反卷积算法研究骨关节炎的免疫机制及潜在中药靶向预测[J].中国免疫学杂志,2022,38(3):288.
[9] 李娜,陶弘武,柳越冬,等.基于生物信息学的溃疡性结肠炎免疫细胞的浸润模式分析[J].中国免疫学杂志,2020,36(24):2966.
[10] QIN Y, WANG Y, MENG F, et al. Identification of biomarkers by machine learning classifiers to assist diagnose rheumatoid arthritis-associated interstitial lung disease[J].Mathematical Biosciences,2018,303(5):75.
[11] LIN X, YANG F, ZHOU L, et al. A support vector machine-recursive feature elimination feature selection method based on artificial contrast variables and mutual information[J].Analytical Technologies in the Biomedical and Life Sciences,2012,910(6):149.
[12] ALAKWAA F M, CHAUDHARY K, GARMIRE L X. Deep learning accurately predicts estrogen receptor status in breast cancer metabolomics data[J].Journal of Proteome Research,2018,17(1):337.
[13] BARDOU P, MARIETTE J, ESCUDIÉ F, et al. Jvenn:an interactive Venn diagram viewer[J].BioMed Central Bioinformatics,2014,15(1):293.
[14] NEWMAN A M, LIU C L, GREEN M R, et al. Robust enumeration of cell subsets from tissue expression profiles[J].Nature Methods,2015,12(5):453.
[15] LUO X, CHEN J, YANG H, et al. Dendritic cell immunoreceptor drives atopic dermatitis by modulating oxidized CaMKII-involved mast cell activation[J].Journal of Clinical Investigation Insight,2022,7(5):152559.
[16] BARNES K C. An update on the genetics of atopic dermatitis:scratching the surface in 2009[J].The Journal of Allergy and Clinical Immunology,2010,125(1):16.
[17] MARTINEZ F O, GORDON S. The M1 and M2 paradigm of macrophage activation:time for reassessment[J].Faculty of 1000 Prime Reports,2014,3(6):13.
[18] HRISTODOROV D, MLADENOV R, VON FELBERT V, et al. Targeting CD64 mediates elimination of M1 but not M2 macrophages in vitro and in cutaneous inflammation in mice and patient biopsies[J].Monoclonal Antibodies,2015,7(5):853.
[19] MACK M R, BRESTOFF J R, BERRIEN-ELLIOTT M M, et al. Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis[J].Science Translational Medicine,2020,12(532):1005.
[20] JIANG J, YAN S, ZHOU X, et al. Crosstalk between circulating follicular T helper cells and regulatory B cells in children with extrinsic atopic dermatitis[J].Frontiers in Immunology,2021,30(12):785549.
[21] CHEN B R, HSU K T, LI T L, et al. Topical application of fucoidan derived from Cladosiphon okamuranus alleviates atopic dermatitis symptoms through immunomodulation[J].International Immunopharmacology,2021,101(23):108362.
[22] ABD-ELAZIZ K, JESENAK M, VASAKOVA M, et al. Revisiting matrix metalloproteinase 12:its role in pathophysiology of asthma and related pulmonary diseases[J].Current Opinion in Pulmonary Medicine,2020,27(1):54.
[23] BRUNNER P M, SUÁREZ-FARIÑAS M, HE H, et al. The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins[J].Scientific Reports,2017,7(1):8707.
[24] GUTTMAN-YASSKY E, BISSONNETTE R, UNGAR B, et al. Dupilumab progressively improves systemic and cutaneous abnormalities in atopic dermatitis patients[J].The Journal of Allergy and Clinical Immunology,2018,143(1):155.
[25] CHAE W J, BOTHWELL A L M. Canonical and non-canonical wnt signaling in immune cells[J].Trends in Immunology,2018,39(10):830.
[26] SCHLÜTER H, STARK H J, SINHA D, et al. WIF1 is expressed by stem cells of the human interfollicular epidermis and acts to suppress keratinocyte proliferation[J].The Journal of Investigative Dermatology,2013,133(6):1669.

备注/Memo

备注/Memo:
收稿日期:2022-09-23
基金项目:国家自然科学基金项目(81972922)
通信作者:吴志宏(1966— ),男,浙江省温州人,研究员,博士,主要从事皮肤天然免疫研究。E-mail:zhihong.wu@zust.edu.cn。
更新日期/Last Update: 2023-12-31