Metabolomic Profiling Reveals That 5-Hydroxylysine and 1-Methylnicotinamide Are Metabolic Indicators of Keloid...

Background: Keloid is a skin fibroproliferative disease with unknown pathogenesis. Metabolomics provides a new perspective for revealing biomarkers related to metabolites and their metabolic mechanisms. Method: Metabolomics and transcriptomics were used for data analysis. Quality control of the data was performed to standardize the data. Principal component analysis (PCA), PLS-DA, OPLS-DA, univariate analysis, CIBERSORT, neural network model, and machine learning correlation analysis were used to calculate differential metabolites. The molecular mechanisms of characteristic metabolites and differentially expressed genes were identified through enrichment analysis and topological analysis. Result: Compared with normal tissue, lipids have a tendency to decrease in keloids, while peptides have a tendency to increase in keloids. Significantly different metabolites between the two groups were identified by random forest analysis, including 1-methylnicotinamide, 4-hydroxyproline, 5-hydroxylysine, and l-prolinamide. The metabolic pathways which play important roles in the pathogenesis of keloids included arachidonic acid metabolism and d-arginine and d-ornithine metabolism. Metabolomic profiling reveals that 5-hydroxylysine and 1-methylnicotinamide are metabolic indicators of keloid severity. The high-risk early warning index for 5-hydroxylysine is 4 × 10⁸-6.3×10⁸ (p = 0.0008), and the high-risk predictive index for 1-methylnicotinamide is 0.95 × 10⁷-1.6×10⁷ (p = 0.0022). Conclusion: This study was the first to reveal the metabolome profile and transcriptome of keloids. Differential metabolites and metabolic pathways were calculated by machine learning. Metabolomic profiling reveals that 5-hydroxylysine and 1-methylnicotinamide may be metabolic indicators of keloid severity.