Single-cell sequencing analysis and bulk-seq identify IGFBP6 and TNFAIP6 as novel differential diagnosis markers for postburn pathological scarring

Single-cell sequencing analysis unveiled 29 and 30 cell clusters in keloids and hypertrophic scars, respectively, predominantly composed of fibroblasts. Bulk differential gene analysis showed 96 highly expressed genes and 69 lowly expressed genes in keloids compared to hypertrophic scars. By incorporating previous research, Gene Set Enrichment Analysis was conducted to select fibroblasts as the focus of research. According to the single-cell data, 301 genes were stably expressed in fibroblasts from both types of pathological scars. Consistently, Weighted Gene Co-expression Network Analysis revealed that the blue module genes were mostly hub genes associated with fibroblasts. After intersecting fibroblast-related genes in single-cell data, Weighted Gene Co-expression Network Analysis-hub module genes, and bulk differential expression genes, insulin-like growth factor binding protein 6 and tumour necrosis factor alpha-induced protein 6 were identified as key genes to distinguish keloids from hypertrophic scars, resulting in diagnostic accuracies of 1.0 and 0.75, respectively. Immunohistochemical Staining and Quantitative Reverse Transcription PCR revealed that the expression levels of tumour necrosis factor alpha induced protein 6 and insulin-like growth factor binding protein 6 were significantly lower in postburn keloids than in hypertrophic scars- CONCLUSIONS: Tumour necrosis factor alpha induced protein 6 and insulin-like growth factor binding protein 6, exhibiting high diagnostic accuracy, provide valuable guidance for the differential diagnosis and treatment of postburn pathological scars.