Integrating multiomics sequencing analyses uncover the key mechanisms related to oxidative stress, mitochondria, and immune cells in keloid.

Abstract

Background: This study aimed to investigate the key molecular mechanisms underlying keloid pathogenesis by integrating oxidative stress, mitochondria, and immune cells.

Methods: Transcriptome sequencing (mRNA, lncRNA, and circRNA expression data), proteomic sequencing, and small RNA sequencing analyses of lesional and non-lesional skin of patients with keloids and healthy control (normal) skin were conducted. By integrating mRNA and publicly available gene expression data (GSE158395), differentially expressed genes related to oxidative stress and mitochondrial function in keloids were identified. Hub genes were identified using various bioinformatics analyses such as immune infiltration analysis, weighted gene co-expression network analysis, machine learning, and expression validation using proteomics sequencing data. Moreover, a competing endogenous RNA (ceRNA) network of hub genes was constructed by combining miRNA, lncRNA, and circRNA expression data. Five hub genes were identified: MGST1, DHCR24, ALDH3A2, ADH1B, and FKBP5.

Results: These hub genes had a high diagnostic value for keloids, with an AUC value > 0.8 each. In addition, five hub genes were associated with the infiltration of multiple immune cells. The immune cells with the strongest positive and negative correlations with hub genes were M0 and M1 macrophages. A ceRNA network was constructed, and several ceRNAs, such as AC005062.1/miR-134-5p/FKBP5 and BASP1-AS1/miR-503-5p/ADH1B, were identified. These five hub genes may contribute to keloid pathogenesis.

Conclusion: These genes and their related ceRNAs may serve as diagnostic biomarkers and therapeutic targets for keloids.