ANKRD46 as a shared diagnostic and therapeutic marker in keloid and type 2 diabetes mellitus identified via multi omics and experimental validation

Background: Keloids and Type 2 diabetes mellitus (T2DM) involve chronic inflammation and impaired wound healing. Exploring their molecular similarities may reveal their shared therapeutic targets. Methods: We conducted a multi-omics analysis utilizing RNA expression data from keloid and T2DM samples. Differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) were applied to identify shared differentially expressed genes (DEGs). Functional enrichment analysis and immune infiltration profiling were performed to elucidate the underlying biological pathways. To identify diagnostic biomarkers, machine learning techniques, including LASSO and SVM-RFE, were employed. The experimental validation of ANKRD46 was carried out using Western blotting, qRT-PCR, IHC, flow cytometry, and the establishment of mouse models. Results: A total of 20 DEGs were found to overlap between keloids and T2DM, with significant enrichment in pathways related to glucose metabolism and immune responses. ANKRD46 emerged as a robust diagnostic marker, demonstrating strong correlations with immune cells, including plasmacytoid dendritic cells and activated B cells. Experimental validation confirmed the upregulation of ANKRD46 in both conditions, with AUC values exceeding 0.75 in diagnostic models. Functional studies further confirmed a strong association between ANKRD46 and the IL6-JAK-STAT3 signaling pathway, with miR-21 regulating its expression within the fibrotic microenvironment. Conclusion: ANKRD46 is a promising shared diagnostic and therapeutic target for keloids and T2DM, with its role in regulating immune responses and fibrosis supported by both computational and experimental data. This study highlights the potential of ANKRD46 in modulating the IL6-JAK-STAT3 pathway, providing a foundation for future therapeutic strategies targeting both diseases.