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胰岛素样生长因子结合蛋白 7 作为系统性硬化症的候选生物标志物。

Insulin-like growth factor binding protein 7 as a candidate biomarker for systemic sclerosis.

机构信息

Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai, and State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, China.

出版信息

Clin Exp Rheumatol. 2021 Jul-Aug;39 Suppl 131(4):66-76. doi: 10.55563/clinexprheumatol/b9j9fd. Epub 2020 Nov 17.

Abstract

OBJECTIVES

Systemic sclerosis (SSc) is an autoimmune disease clinically characterised by skin and internal organs fibrosis with high mortality. However, the pathogenesis of SSc is still controversial and the effect of the current treatment is far from satisfactory. We aimed to find out novel candidate genes related to the pathological process in SSc.

METHODS

In this study, the weighted correlation network analysis (WGCNA) was conducted to identify the key module and hub genes most related to SSc in GSE58095, a microarray dataset from the Gene Expression Omnibus (GEO) database. Also, the key module was analysed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then we validated hub genes in other datasets (GSE32413, GSE125362, GSE45485, GSE76885, GSE95065). The serum of 37 patients with SSc and 25 healthy control subjects (HCs) were recruited and detected by Enzyme-Linked Immunosorbent Assay (ELISA).

RESULTS

Five interested genes (IGFBP7, LRRC32, STMN2, C1QTNF5, CPXM1) were up-regulated in SSc microarray datasets from the GEO. And the level of serum IGFBP7, which encodes a secreted protein, was upregulated in SSc patients-also in dcSSc patients and SSc with ILD patients.

CONCLUSIONS

Among the five interested genes, the IGFBP7 was a novel candidate gene for SSc and may be served as potential target and early biomarker for accurate treatment, which also provides further insights into the pathogenesis of SSc at the molecular level.

摘要

目的

系统性硬化症(SSc)是一种自身免疫性疾病,临床上以皮肤和内脏器官纤维化为特征,死亡率高。然而,SSc 的发病机制仍存在争议,目前的治疗效果远不理想。我们旨在寻找与 SSc 病理过程相关的新候选基因。

方法

本研究采用加权相关网络分析(WGCNA),从基因表达综合数据库(GEO)的 GSE58095 微阵列数据集识别与 SSc 最相关的关键模块和枢纽基因。此外,通过基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)分析对关键模块进行分析。然后在其他数据集(GSE32413、GSE125362、GSE45485、GSE76885、GSE95065)中验证枢纽基因。收集 37 例 SSc 患者和 25 例健康对照(HC)的血清,采用酶联免疫吸附试验(ELISA)进行检测。

结果

在 GEO 的 SSc 微阵列数据集中,有 5 个感兴趣的基因(IGFBP7、LRRC32、STMN2、C1QTNF5、CPXM1)上调。其中,编码分泌蛋白的 IGFBP7 血清水平在 SSc 患者中上调,在 dcSSc 患者和 SSc 合并ILD 患者中也上调。

结论

在这 5 个感兴趣的基因中,IGFBP7 是 SSc 的一个新候选基因,可能作为潜在的治疗靶点和早期生物标志物,为 SSc 在分子水平上的发病机制提供了进一步的认识。

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