Identification of Key Modules and Hub Genes of Keloids with Weighted Gene Coexpression Network Analysis.

Abstract

Keloid scarring impairs patients' quality of life, and although many therapeutic strategies have been developed, most remain unsatisfactory because of limited understanding of the mechanisms underlying keloid development. A microarray gene expression data set from keloid tissue was acquired from the Gene Expression Omnibus. Differentially expressed genes in fibroblasts and keratinocytes underwent functional annotation and pathway analysis. Weighted gene coexpression network analysis was applied to identify the gene targets of keloid scars within differentially expressed genes. Modules and hub genes for keloids were identified. Enrichment analysis was undertaken to verify the modules' and hub genes' relationship with keloids. Enrichment analysis and pathway analysis showed gene ontology terms and pathways related to keloids. Each cell type generated three modules in weighted gene coexpression network analysis, with one module most related to keloids. Enrichment analysis showed that the modules concerned are enriched with terms related to keloids. Three hub genes were selected for fibroblasts and keratinocytes, and their relationship to keloids was verified. Immunohistochemical staining verified expression change of some hub genes. This is the first study to describe the gene networks underlying keloids. Modules and hub genes generated in the present study are highly related to keloids and may identify novel therapeutic targets for treatment of keloids. Therapeutic, V.