Comparative analysis of affected and unaffected areas of systemic sclerosis skin biopsies by high-throughput proteomic approaches

Abstract Background 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 com...

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Main Authors: Paraskevi Chairta, Paschalis Nicolaou, Kleitos Sokratous, Christine Galant, Frédéric Houssiau, Anastasis Oulas, George M. Spyrou, Marta E. Alarcon-Riquelme, Bernard R. Lauwerys, Kyproula Christodoulou
Format: Article
Language:English
Published: BMC 2020-05-01
Series:Arthritis Research & Therapy
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13075-020-02196-x
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author Paraskevi Chairta
Paschalis Nicolaou
Kleitos Sokratous
Christine Galant
Frédéric Houssiau
Anastasis Oulas
George M. Spyrou
Marta E. Alarcon-Riquelme
Bernard R. Lauwerys
Kyproula Christodoulou
author_facet Paraskevi Chairta
Paschalis Nicolaou
Kleitos Sokratous
Christine Galant
Frédéric Houssiau
Anastasis Oulas
George M. Spyrou
Marta E. Alarcon-Riquelme
Bernard R. Lauwerys
Kyproula Christodoulou
author_sort Paraskevi Chairta
collection DOAJ
description Abstract Background 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. Methods 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. Results 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. Conclusion 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.
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spelling doaj.art-776684f593b243b6ae395cd485ba31382022-12-22T00:46:36ZengBMCArthritis Research & Therapy1478-63622020-05-012211910.1186/s13075-020-02196-xComparative analysis of affected and unaffected areas of systemic sclerosis skin biopsies by high-throughput proteomic approachesParaskevi Chairta0Paschalis Nicolaou1Kleitos Sokratous2Christine Galant3Frédéric Houssiau4Anastasis Oulas5George M. Spyrou6Marta E. Alarcon-Riquelme7Bernard R. Lauwerys8Kyproula Christodoulou9Cyprus School of Molecular MedicineCyprus School of Molecular MedicineCyprus School of Molecular MedicineDepartment of Pathology, Université catholique de LouvainRheumatology Department, Cliniques Universitaires Saint-Luc, Pôle de Pathologies Rhumatismales Inflammatoires et Systémiques, Université catholique de LouvainCyprus School of Molecular MedicineCyprus School of Molecular MedicineArea of Medical Genomics, Pfizer–Universidad de Granada–Junta de Andalucía de Genómica e Investigación Oncológica (GENyO), Parque Tenológico de la Salud Fundación (PTS) Granada, Spain; Arthritis and Clinical Immunology, Oklahoma Medical Research FoundationDepartment of Pathology, Université catholique de LouvainCyprus School of Molecular MedicineAbstract Background 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. Methods 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. Results 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. Conclusion 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.http://link.springer.com/article/10.1186/s13075-020-02196-xSystemic sclerosisSclerodermaBiomarkersProteomicsMass spectrometryRheumatology
spellingShingle Paraskevi Chairta
Paschalis Nicolaou
Kleitos Sokratous
Christine Galant
Frédéric Houssiau
Anastasis Oulas
George M. Spyrou
Marta E. Alarcon-Riquelme
Bernard R. Lauwerys
Kyproula Christodoulou
Comparative analysis of affected and unaffected areas of systemic sclerosis skin biopsies by high-throughput proteomic approaches
Arthritis Research & Therapy
Systemic sclerosis
Scleroderma
Biomarkers
Proteomics
Mass spectrometry
Rheumatology
title Comparative analysis of affected and unaffected areas of systemic sclerosis skin biopsies by high-throughput proteomic approaches
title_full Comparative analysis of affected and unaffected areas of systemic sclerosis skin biopsies by high-throughput proteomic approaches
title_fullStr Comparative analysis of affected and unaffected areas of systemic sclerosis skin biopsies by high-throughput proteomic approaches
title_full_unstemmed Comparative analysis of affected and unaffected areas of systemic sclerosis skin biopsies by high-throughput proteomic approaches
title_short Comparative analysis of affected and unaffected areas of systemic sclerosis skin biopsies by high-throughput proteomic approaches
title_sort comparative analysis of affected and unaffected areas of systemic sclerosis skin biopsies by high throughput proteomic approaches
topic Systemic sclerosis
Scleroderma
Biomarkers
Proteomics
Mass spectrometry
Rheumatology
url http://link.springer.com/article/10.1186/s13075-020-02196-x
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