Identification of Genes and Pathways Associated with Acne Using Integrated Bioinformatics Methods

Abstract

Background: Acne is the most common skin inflammatory condition. The pathogenesis of acne is not fully understood. Aims: We performed weighted gene co-expression network analysis (WGCNA) to select acne-associated genes and pathways. Methods: GSE53795 and GSE6475 datasets including data from lesional and nonlesional skin of acne patients were downloaded from the NCBI Gene Expression Omnibus. Differentially expressed genes (DEGs) in lesions were identified following a false discovery rate <0.05 and | log2 fold change | ≥0.5. DEG-associated biological processes and pathways were identified. WGCNA analysis was performed to identify acne-associated modules. DEGs in the acne-associated modules were used for protein-protein interaction (PPI) network construction and Gene Set Enrichment Analysis (GSEA). Acne-associated candidate DEGs and pathways were identified together with items in the Comparative Toxicogenomics Database (CTD). Results: A total of 2,140 and 1,190 DEGs were identified in GSE53795 and GSE6475 datasets, respectively, including 716 overlapping DEGs with similar expression profiles in the two datasets, which were clustered into 10 consensus modules. Two modules (brown and turquoise, 359 genes) were associated with acne phenotype. Of these 359 DEGs, 254 were enrolled in the PPI network. GSEA showed that these DEGs were associated with chemokine signaling pathway, cytokine-cytokine receptor interaction, and natural killer cell-mediated cytotoxicity. After identification in CTD, one pathway Cytokine-cytokine receptor interaction and 24 acne-associated DEGs, including IL1R1, CXCL1, CXCR4, CCR1, CXCL2 and IL1β, were identified as candidates associated with acne. Conclusion: Our results highlight the important roles of the proinflammatory cytokines including IL1β, CXCL1, CXCL2, CXCR4, and CCR1 in acne pathogenesis or therapeutic management.

Review—Current Concepts in Inflammatory Skin Diseases Evolved by Transcriptome Analysis: In-Depth Analysis of Atopic Dermatitis and Psoriasis

“…Through analyzing bacterial metabolic pathways, this approach led to a potential mechanism of supplemented VitB12-induced acne [121]. WGCNA was utilized to construct interaction networks which highlight the role of central cytokines in the disease's pathophysiology (e.g., IL1β and CXCl1/2) [122,123]. Recently, the role of miRNAs was also introduced into this research field as depicted in Table A2 [124,125].…”

Use of bioinformatic analyses in identifying characteristic genes and mechanisms active in the progression of idiopathic thrombocytopenic purpura in individuals with different phenotypes

“…Several studies have previously explored biomarkers using a combination of WGCNA and DEG identification to ensure reliability. [30][31][32] Therefore, a similar integrated method of analysis was used in our study, and characteristic genes in the chronic ITP group were shown to be Figure 6. Sub-network of hub genes related to the disease phenotype of chronic ITP.…”

PEG-8 Laurate Fermentation of Staphylococcus epidermidis Reduces the Required Dose of Clindamycin Against Cutibacterium acnes

“…Detection of C. acnes induced inflammatory cytokines provides a validation on effective inhibition on C. acnes growth. CXCL1/keratinocyte-derived chemokine (KC), CXCL2/MIP2 and CXCL5-6/lipopolysaccharide-induced CXC chemokine (LIX) were regarded as functional homologues of IL-8, where CXCL1, CXCL2 and CXCL6 are identified as candidates associated with acne pathogenesis in humans [39,40]. Additionally, multiple studies in the mouse acne model showed a remarkable increase in the production of neutrophils, macrophages and MIP-2 upon C. acnes administration into mice [41][42][43].…”