Cross-Comparison of Inflammatory Skin Disease Transcriptomics Identifies PTEN as a Pathogenic Disease Classifier in Cutaneous Lupus Erythematosus.

Autor:	Aevermann BD; J. Craig Venter Institute, La Jolla, California, USA; Chan Zuckerberg Initiative, Redwood City, California, USA., Di Domizio J; Department of Dermatology, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland., Olah P; Department of Dermatology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Saidoune F; Department of Dermatology, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland., Armstrong JM; Galderma, Lausanne, Switzerland., Bachelez H; Department of Dermatology, Paris Diderot University, Paris, France., Barker J; St John's Institute of Dermatology, Faculty of Life Sciences & Medicine, Kings College London, London, United Kingdom., Haniffa M; Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle, United Kingdom., Julia V; Galderma, Lausanne, Switzerland., Juul K; LEO Pharma A/S, Ballerup, Denmark., Krishnaswamy JK; Galderma, Lausanne, Switzerland., Litman T; LEO Pharma A/S, Ballerup, Denmark., Parsons I; Celgene International Sarl, Boudry, Switzerland., Sarin KY; Department of Dermatology, Stanford University Medical Center, Palo Alto, California, USA., Schmuth M; Department of Dermatology, Venereology and Allergy, Medical University Innsbruck, Innsbruck, Austria., Sierra M; LEO Pharma A/S, Ballerup, Denmark., Simpson M; Department of Genomic Medicine, King's College London, London, United Kingdom., Homey B; Department of Dermatology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Griffiths CEM; Section of Dermatology, Department of Medicine, University of Manchester, Manchester, United Kingdom., Scheuermann RH; J. Craig Venter Institute, La Jolla, California, USA; Department of Pathology, University of California San Diego School of Medicine, La Jolla, California, USA; La Jolla Institute for Immunology, La Jolla, California, USA., Gilliet M; Department of Dermatology, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland. Electronic address: michel.gilliet@chuv.ch.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2024 Feb; Vol. 144 (2), pp. 252-262.e4. Date of Electronic Publication: 2023 Aug 19.
DOI:	10.1016/j.jid.2023.06.211
Abstrakt:	Tissue transcriptomics is used to uncover molecular dysregulations underlying diseases. However, the majority of transcriptomics studies focus on single diseases with limited relevance for understanding the molecular relationship between diseases or for identifying disease-specific markers. In this study, we used a normalization approach to compare gene expression across nine inflammatory skin diseases. The normalized datasets were found to retain differential expression signals that allowed unsupervised disease clustering and identification of disease-specific gene signatures. Using the NS-Forest algorithm, we identified a minimal set of biomarkers and validated their use as diagnostic disease classifier. Among them, PTEN was identified as being a specific marker for cutaneous lupus erythematosus and found to be strongly expressed by lesional keratinocytes in association with pathogenic type I IFNs. In fact, PTEN facilitated the expression of IFN-β and IFN-κ in keratinocytes by promoting activation and nuclear translocation of IRF3. Thus, cross-comparison of tissue transcriptomics is a valid strategy to establish a molecular disease classification and to identify pathogenic disease biomarkers. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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