Cyprus School of Molecular Medicine, 6 Iroon Avenue, 2371, Nicosia, Cyprus.
Neurogenetics Department, Cyprus Institute of Neurology & Genetics, 6 Iroon Avenue, 2371, Nicosia, Cyprus.
Arthritis Res Ther. 2020 May 7;22(1):107. doi: 10.1186/s13075-020-02196-x.
Pathogenesis and aetiology of systemic sclerosis (SSc) are currently unclear, thus rendering disease prognosis, diagnosis and treatment challenging. The aim of this study was to use paired skin biopsy samples from affected and unaffected areas of the same patient, in order to compare the proteomes and identify biomarkers and pathways which are associated with SSc pathogenesis.
Biopsies were obtained from affected and unaffected skin areas of SSc patients. Samples were cryo-pulverised and proteins were extracted and analysed using mass spectrometry (MS) discovery analysis. Differentially expressed proteins were revealed after analysis with the Progenesis QIp software. Pathway analysis was performed using the Enrichr Web server. Using specific criteria, fifteen proteins were selected for further validation with targeted-MS analysis.
Proteomic analysis led to the identification and quantification of approximately 2000 non-redundant proteins. Statistical analysis showed that 169 of these proteins were significantly differentially expressed in affected versus unaffected tissues. Pathway analyses showed that these proteins are involved in multiple pathways that are associated with autoimmune diseases (AIDs) and fibrosis. Fifteen of these proteins were further investigated using targeted-MS approaches, and five of them were confirmed to be significantly differentially expressed in SSc affected versus unaffected skin biopsies.
Using MS-based proteomics analysis of human skin biopsies from patients with SSc, we identified a number of proteins and pathways that might be involved in SSc progression and pathogenesis. Fifteen of these proteins were further validated, and results suggest that five of them may serve as potential biomarkers for SSc.
系统性硬化症（SSc）的发病机制和病因目前尚不清楚，因此疾病的预后、诊断和治疗极具挑战性。本研究旨在使用同一患者病变和非病变皮肤的配对活检样本，比较蛋白质组并确定与 SSc 发病机制相关的生物标志物和途径。
从 SSc 患者的病变和非病变皮肤区域获取活检。将样本冷冻粉碎，使用质谱（MS）发现分析提取和分析蛋白质。使用 Progenesis QIp 软件分析后揭示差异表达蛋白。使用 Enrichr Web 服务器进行途径分析。使用特定标准，选择十五种蛋白质进行靶向-MS 分析的进一步验证。
蛋白质组学分析确定和定量了大约 2000 种非冗余蛋白。统计分析表明，这些蛋白中有 169 种在病变与非病变组织中差异表达显著。途径分析表明，这些蛋白涉及与自身免疫性疾病（AIDs）和纤维化相关的多个途径。使用靶向-MS 方法进一步研究了这 15 种蛋白质，其中 5 种在 SSc 病变与非病变皮肤活检中差异表达显著。
通过对 SSc 患者皮肤活检的 MS 蛋白质组学分析，我们确定了一些可能参与 SSc 进展和发病机制的蛋白质和途径。进一步验证了这 15 种蛋白质，结果表明其中 5 种可能作为 SSc 的潜在生物标志物。
