# Identify Diagnostic Biomarkers Related to Taurine Metabolism in Diabetic Foot Ulcers Using Bulk RNA‐seq and ScRNA‐seq Analysis

## TL;DR

This study identifies three genes linked to taurine metabolism that can accurately diagnose diabetic foot ulcers and explores immune and cellular changes in the condition.

## Contribution

A novel three-gene diagnostic signature (HMOX1, MAPK3, TXN) with near-perfect accuracy for diabetic foot ulcers is identified using multi-omics and single-cell RNA-seq.

## Key findings

- A three-gene diagnostic signature (HMOX1, MAPK3, TXN) achieved AUC = 1 in training and AUC ≥ 0.98 in validation.
- Immune dysregulation in DFU includes increased B cells, CD8+ T cells, and M1 macrophages.
- Single-cell RNA-seq revealed fibroblast and endothelial cell expansion in DFU, with HMOX1 in macrophages and MAPK3 in endothelium.

## Abstract

Diabetic foot ulcers (DFU) are severe complications with complex pathogenesis involving inflammation and impaired healing. Taurine, a key antioxidant amino acid, shows therapeutic potential in diabetes, but its role in DFU remains unclear and warrants investigation.

This integrated multi‐omics study analyzed DFU using GEO transcriptomics data (training: GSE68183/GSE80178; validation: GSE37265/GSE134431; scRNA‐seq: GSE223964). Limma identified DEGs that intersected with taurine metabolism ‐related genes. Key modules (MCODE) and a LASSO‐based diagnostic signature were established. Immune infiltration was profiled via ssGSEA, CIBERSORT, and MCP‐Counter. Regulatory networks (TFs/miRNAs) were predicted (miRNet/NetworkAnalyst), and therapeutic agents were screened (DSigDB). Seurat‐processed scRNA‐seq defined nine cell types, with CellChat analyzing intercellular communication.

This study identified a three‐gene diagnostic signature (HMOX1, MAPK3, TXN) for DFU with near‐perfect accuracy (training AUC = 1, validation AUC ≥ 0.98). Multi‐omics analyses revealed significant immune dysregulation (increased B cells/CD8+T cells/M1 macrophages in DFS), collagen‐centric signaling dominance, and two molecular subtypes. Single‐cell RNA‐seq uncovered cell‐type‐specific dysfunction: fibroblasts and endothelial cells expanded in DFS, while HMOX1 localized to Mono‐macrophages and MAPK3 to endothelium.

This study deeply analyzed DFU immune microenvironment characteristics, intercellular communication networks, and molecular regulatory mechanisms, revealing a dysregulated metabolic–immune repair network framework, providing new insights for understanding DFU pathological mechanisms and developing targeted diagnostic and therapeutic strategies.

This figure comprehensively showcases the study's core findings—exceptional diagnostic performance (AUC = 1) of the taurine metabolism‐related biomarkers (HMOX1, MAPK3, TXN) in DFU, validated across independent cohorts. It integrates ROC curves, decision curve analysis (DCA), and nomograms, visually summarizing the translational potential of the research.