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Molecular Subsets in the Gene Expression Signatures of Scleroderma Skin

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Listed:
  • Ausra Milano
  • Sarah A Pendergrass
  • Jennifer L Sargent
  • Lacy K George
  • Timothy H McCalmont
  • M Kari Connolly
  • Michael L Whitfield

Abstract

Background: Scleroderma is a clinically heterogeneous disease with a complex phenotype. The disease is characterized by vascular dysfunction, tissue fibrosis, internal organ dysfunction, and immune dysfunction resulting in autoantibody production. Methodology and Findings: We analyzed the genome-wide patterns of gene expression with DNA microarrays in skin biopsies from distinct scleroderma subsets including 17 patients with systemic sclerosis (SSc) with diffuse scleroderma (dSSc), 7 patients with SSc with limited scleroderma (lSSc), 3 patients with morphea, and 6 healthy controls. 61 skin biopsies were analyzed in a total of 75 microarray hybridizations. Analysis by hierarchical clustering demonstrates nearly identical patterns of gene expression in 17 out of 22 of the forearm and back skin pairs of SSc patients. Using this property of the gene expression, we selected a set of ‘intrinsic’ genes and analyzed the inherent data-driven groupings. Distinct patterns of gene expression separate patients with dSSc from those with lSSc and both are easily distinguished from normal controls. Our data show three distinct patient groups among the patients with dSSc and two groups among patients with lSSc. Each group can be distinguished by unique gene expression signatures indicative of proliferating cells, immune infiltrates and a fibrotic program. The intrinsic groups are statistically significant (p

Suggested Citation

  • Ausra Milano & Sarah A Pendergrass & Jennifer L Sargent & Lacy K George & Timothy H McCalmont & M Kari Connolly & Michael L Whitfield, 2008. "Molecular Subsets in the Gene Expression Signatures of Scleroderma Skin," PLOS ONE, Public Library of Science, vol. 3(7), pages 1-19, July.
  • Handle: RePEc:plo:pone00:0002696
    DOI: 10.1371/journal.pone.0002696
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    1. Charles M. Perou & Therese Sørlie & Michael B. Eisen & Matt van de Rijn & Stefanie S. Jeffrey & Christian A. Rees & Jonathan R. Pollack & Douglas T. Ross & Hilde Johnsen & Lars A. Akslen & Øystein Flu, 2000. "Molecular portraits of human breast tumours," Nature, Nature, vol. 406(6797), pages 747-752, August.
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    1. Xiao Xu & Meera Ramanujam & Sudha Visvanathan & Shervin Assassi & Zheng Liu & Li Li, 2020. "Transcriptional insights into pathogenesis of cutaneous systemic sclerosis using pathway driven meta-analysis assisted by machine learning methods," PLOS ONE, Public Library of Science, vol. 15(11), pages 1-20, November.
    2. Luca Beltrame & Lisa Rizzetto & Raffaele Paola & Philippe Rocca-Serra & Luca Gambineri & Cristina Battaglia & Duccio Cavalieri, 2009. "Using Pathway Signatures as Means of Identifying Similarities among Microarray Experiments," PLOS ONE, Public Library of Science, vol. 4(1), pages 1-11, January.
    3. J Matthew Mahoney & Jaclyn Taroni & Viktor Martyanov & Tammara A Wood & Casey S Greene & Patricia A Pioli & Monique E Hinchcliff & Michael L Whitfield, 2015. "Systems Level Analysis of Systemic Sclerosis Shows a Network of Immune and Profibrotic Pathways Connected with Genetic Polymorphisms," PLOS Computational Biology, Public Library of Science, vol. 11(1), pages 1-20, January.
    4. Sarah A Pendergrass & Everett Hayes & Giuseppina Farina & Raphael Lemaire & Harrison W Farber & Michael L Whitfield & Robert Lafyatis, 2010. "Limited Systemic Sclerosis Patients with Pulmonary Arterial Hypertension Show Biomarkers of Inflammation and Vascular Injury," PLOS ONE, Public Library of Science, vol. 5(8), pages 1-13, August.

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