ORIGINAL RESEARCH article

Front. Genet.

Sec. Computational Genomics

Volume 16 - 2025 | doi: 10.3389/fgene.2025.1620749

An analysis of gene expression profiles through machine learning uncovers the new diagnostic signature for diabetic foot ulcers

Provisionally accepted
Yingnan  LiYingnan Li1*Ning  XiaoNing Xiao2Zhuoqun  WangZhuoqun Wang1Wenhai  WangWenhai Wang1Fengjiao  LiFengjiao Li2Jiren  WangJiren Wang2
  • 1Jilin Province FAW General Hospital, Chuangchun, China
  • 2Jilin Province FAW General Hospital, Changchun, China

The final, formatted version of the article will be published soon.

Purpose: Diabetic foot ulcers (DFUs), a serious diabetes complication, greatly increase disability and mortality, underscoring the need for effective diagnostic markers.Methods: We used GSE199939 and GSE134431 datasets from the Gene Expression Omnibus (GEO) database, removed batch effects, and identified differentially expressed genes (DEGs). The weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules, followed by the integration of the protein-protein interaction (PPI) network to screen key genes, which were further optimized using LASSO regression. The gene set enrichment analysis (GSEA) analyzed key gene-related pathways, CIBERSORT assessed immune infiltration, and potential target drugs were predicted using the DGIdb database.Results: We identified 403 DEGs in DFUs, intersected them with 2,342 genes from a DFU-related WGCNA module to find 193 overlapping genes, and screened candidates via PPI network. LASSO regression finalized DCT, PMEL, and KIT as the key genes. GSEA analysis showed these three genes may influence the MAPK and PI3K-Akt pathways and were positively correlated with Dendritic.cells.resting. Drug target prediction identified 85 potential drugs for KIT, six for DCT, and six for PMEL.Conclusions: This research highlights DCT, PMEL, and KIT as diagnostic biomarkers for DFUs, which are linked to melanin production and the MAPK/PI3K-Akt signaling pathways.

Keywords: Diabetic foot ulcers, WGCNA, PPI Network, Melanin synthesis, diagnosis

Received: 01 May 2025; Accepted: 05 Jun 2025.

Copyright: © 2025 Li, Xiao, Wang, Wang, Li and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yingnan Li, Jilin Province FAW General Hospital, Chuangchun, China

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