Dataset Information

Transcriptome Meta-Analysis Confirms the Hidradenitis Suppurativa Pathogenic Triad: Upregulated Inflammation, Altered Epithelial Organization, and Dysregulated Metabolic Signaling.

ABSTRACT: Hidradenitis suppurativa (HS) is an inflammatory skin condition clinically characterized by recurrent painful deep-seated nodules, abscesses, and sinus tracks in areas bearing apocrine glands, such as axillae, breasts, groins, and buttocks. Despite many recent advances, the pathophysiological landscape of HS still demands further clarification. To elucidate HS pathogenesis, we performed a meta-analysis, set analysis, and a variant calling on selected RNA-Sequencing (RNA-Seq) studies on HS skin. Our findings corroborate the HS triad composed of upregulated inflammation, altered epithelial differentiation, and dysregulated metabolism signaling. Upregulation of specific genes, such as KRT6, KRT16, serpin-family genes, and SPRR3 confirms the early involvement of hair follicles and the impairment of barrier function in HS lesioned skin. In addition, our results suggest that adipokines could be regarded as biomarkers of HS and metabolic-related disorders. Finally, the RNA-Seq variant calling identified several mutations in HS patients, suggesting potential new HS-related genes associated with the sporadic form of this disease. Overall, this study provides insights into the molecular pathways involved in HS and identifies potential HS-related biomarkers.

SUBMITTER: de Oliveira ASLE

PROVIDER: S-EPMC9599370 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Transcriptome Meta-Analysis Confirms the Hidradenitis Suppurativa Pathogenic Triad: Upregulated Inflammation, Altered Epithelial Organization, and Dysregulated Metabolic Signaling.

de Oliveira Ana Sofia Lima Estevao ASLE Bloise Giovanna G Moltrasio Chiara C Coelho Antonio A Agrelli Almerinda A Moura Ronald R Tricarico Paola Maura PM Jamain Stéphane S Marzano Angelo Valerio AV Crovella Sergio S Cavalcanti Brandão Lucas André LA

Biomolecules 20220925 10

Hidradenitis suppurativa (HS) is an inflammatory skin condition clinically characterized by recurrent painful deep-seated nodules, abscesses, and sinus tracks in areas bearing apocrine glands, such as axillae, breasts, groins, and buttocks. Despite many recent advances, the pathophysiological landscape of HS still demands further clarification. To elucidate HS pathogenesis, we performed a meta-analysis, set analysis, and a variant calling on selected RNA-Sequencing (RNA-Seq) studies on HS skin. ...[more]

PMID: 36291580

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Project description:Background: The pathogenesis of hidradenitis suppurativa (HS) is not fully understood. This systematic review examined the latest evidence for molecular inflammatory pathways involved in HS as a chronic inflammatory skin disease. Methods: A systematic literature search was performed in PubMed/Medline and EMBASE from January 2013 through September 2017, according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Findings on HS pathogenesis were also compared with those of other immune-mediated inflammatory diseases (IMIDs) in a non-systematic review. In addition, current therapeutic options for HS are briefly discussed on the basis of the findings for the inflammatory pathways involved in HS. Results: A total of 32 eligible publications were identified by the systematic search; these were supplemented with three additional publications. The extracted data indicated that four key themes underlie the pathogenesis of HS and related syndromic conditions. First, nicastrin (NCSTN) and PSTPIP1 mutations are directly associated with auto-inflammatory disease. Secondly, the up-regulation of several cytokines including tumor necrosis factor-α and T helper-17/interleukin-23 are connected to auto-inflammatory mechanisms in the pathogenesis of HS. Thirdly, the microbiome of lesional skin differs significantly vs. normal-appearing skin. Fourthly, HS risk is enhanced through physiological and environmental factors such as smoking, obesity, and mechanical friction. There is significant overlap between the pathogenesis of HS, its syndromic forms and other IMIDs, particularly with respect to aberrations in the innate immune response. Conclusions: The evidence presented in this review supports HS as an auto-inflammatory skin disorder associated with alterations in the innate immune system. Based on these most recent data, an integrative viewpoint is presented on the pathogenesis of HS. Current management strategies on HS consist of anti-inflammatory therapies, surgical removal of chronic lesions, and lifestyle changes such as smoking cessation and weight loss. As large gaps remain in the understanding of the pathogenesis of HS, further research is warranted to ultimately improve the management and treatment of patients with HS and related syndromic conditions.

Project description:BackgroundHidradenitis suppurativa (HS) is a chronic, inflammatory and common skin disease. Observation studies have reported the association between HS and cancers, however no studies reported whether a causal relationship exists between HS and cancers. This study aimed to explore the causal relationship between HS and differential subtypes of cancers by conducting a bidirectional Mendelian randomization (MR) analysis.MethodGenome-wide association study (GWAS) data related to HS and 16 subtypes of cancers were collected. The inverse variance weighted (IVW) method was primarily applied for our MR analysis, MR-Egger, weighted median, simple mode, and weighted mode methods were used additionally. Heterogeneity, horizontal pleiotropy, and potential outliers were assessed for the MR analysis results. Subsequently, disease-related genes were retrieved from the GeneCards database. To investigate the potential functions of these associated genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted.ResultThe results of our MR analysis indicated a causal association between HS and pancreatic cancer (PAC). Specifically, HS was found to elevate the risk of developing PAC (odds ratio (OR), 1.074; 95% confidence interval (CI) 1.015-1.135; p = 0.013). Conversely, reverse MR analysis demonstrated that PAC does not exert a causal effect on HS. Furthermore, our findings did not reveal any significant causal relationships between HS and other types of cancer. No evidence of heterogeneity or pleiotropy was identified in the analysis. Additionally, we identified disease-related genes, and subsequent GO and KEGG enrichment analyses indicated that the genes common to both HS and PAC are implicated in pathways associated with immune and inflammatory processes.ConclusionThe results of this study offer novel evidence regarding the causal relationship between HA and PAC. Our Mendelian randomization analysis indicates that HS may have a causal influence on PAC, which could inform the development of improved treatment strategies for patients suffering from HS. However, the underlying mechanisms warrant further exploration.

Dataset Information

Transcriptome Meta-Analysis Confirms the Hidradenitis Suppurativa Pathogenic Triad: Upregulated Inflammation, Altered Epithelial Organization, and Dysregulated Metabolic Signaling.

Publications

Transcriptome Meta-Analysis Confirms the Hidradenitis Suppurativa Pathogenic Triad: Upregulated Inflammation, Altered Epithelial Organization, and Dysregulated Metabolic Signaling.

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