Objective: The aim of this study was to examine the gene expression signatures of 2 types of excessive scarring, keloid and hypertrophic scar (HS), through the integrated bioinformatics analysis of multiple published gene expression profile datasets.
Methods: A literature search of microarray data published in focusing on keloid and HS was performed. The microarray data were reanalyzed to identify the common significantly dysregulated (CSD) genes. The experimental and statistical parameters of the studies were systematically evaluated to reveal any influences on the consensus findings among the studies. Overrepresentation analysis of gene ontology (GO) categories and pathways was used to explore the significantly dysregulated genes functionally associated with the pathogenesis of excessive scarring.
Results: Seven published microarray studies on keloid and 4 studies on HS were identified. A total of 64 CSD genes were identified in keloid; 9 upregulated CSD genes were identified in HS. The 48 consistently dysregulated genes that overlapped in least 1 keloid study and 1 HS study were defined as the CSD genes in excessive scarring. The differences in the variables associated with the study protocols and data management were systematically documented and evaluated. Activated GO categories and pathways related to skeletal development, binding, extracellular matrix-receptor interaction, and adhesion were found to have significance in excessive scarring, implying a common pathological basis for keloid and HS formation. Notably, the GO categories related to cancer and the TGF-beta signaling pathway were significantly enriched in keloids.
Conclusions: As gene signatures and molecular markers of excessive scarring, the identified CSD genes may be particularly relevant to disease pathogenesis and serve as new therapeutic targets.