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Cross-Comparison of Inflammatory Skin Disease Transcriptomics Identifies PTEN as a Pathogenic Disease Classifier in Cutaneous Lupus Erythematosus.
- Source :
-
The Journal of investigative dermatology [J Invest Dermatol] 2024 Feb; Vol. 144 (2), pp. 252-262.e4. Date of Electronic Publication: 2023 Aug 19. - Publication Year :
- 2024
-
Abstract
- 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.<br /> (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Biomarkers metabolism
Gene Expression Profiling
Keratinocytes metabolism
PTEN Phosphohydrolase genetics
Skin pathology
Dermatitis pathology
Lupus Erythematosus, Cutaneous diagnosis
Lupus Erythematosus, Cutaneous genetics
Lupus Erythematosus, Cutaneous metabolism
Lupus Erythematosus, Systemic genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1747
- Volume :
- 144
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of investigative dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 37598867
- Full Text :
- https://doi.org/10.1016/j.jid.2023.06.211