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

PurposeDiabetic foot ulcers (DFUs), a serious diabetes complication, greatly increase disability and mortality, underscoring the need for effective diagnostic markers.MethodsWe used GSE199939 and GSE134431 datasets from the Gene Expression Omnibus (GEO) database, removed batch effects, and identifie...

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Main Authors: Yingnan Li, Ning Xiao, Zhuoqun Wang, Wenhai Wang, Fengjiao Li, Jiren Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2025.1620749/full
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author Yingnan Li
Ning Xiao
Zhuoqun Wang
Wenhai Wang
Fengjiao Li
Jiren Wang
author_facet Yingnan Li
Ning Xiao
Zhuoqun Wang
Wenhai Wang
Fengjiao Li
Jiren Wang
author_sort Yingnan Li
collection DOAJ
description PurposeDiabetic foot ulcers (DFUs), a serious diabetes complication, greatly increase disability and mortality, underscoring the need for effective diagnostic markers.MethodsWe 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.ResultsWe 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.ConclusionThis research highlights DCT, PMEL, and KIT as diagnostic biomarkers for DFUs, which are linked to melanin production and the MAPK/PI3K-Akt signaling pathways.
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spelling doaj-art-22e9d62aaf064cb3a4ef96bfa47f2f1d2025-08-20T03:16:12ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-06-011610.3389/fgene.2025.16207491620749An analysis of gene expression profiles through machine learning uncovers the new diagnostic signature for diabetic foot ulcersYingnan Li0Ning Xiao1Zhuoqun Wang2Wenhai Wang3Fengjiao Li4Jiren Wang5Hand and Foot Surgery and Burn and Plastic Surgery, Jilin Province FAW General Hospital, Changchun, Jilin, ChinaOffice of Clinical Trial Institutions, Jilin Province FAW General Hospital, Changchun, Jilin, ChinaDepartment of Neurology, Jilin Province FAW General Hospital, Changchun, Jilin, ChinaDepartment of Cardiology, Jilin Province FAW General Hospital, Changchun, Jilin, ChinaDepartment of Anesthesiology, Jilin Province FAW General Hospital, Changchun, Jilin, ChinaHand and Foot Surgery and Burn and Plastic Surgery, Jilin Province FAW General Hospital, Changchun, Jilin, ChinaPurposeDiabetic foot ulcers (DFUs), a serious diabetes complication, greatly increase disability and mortality, underscoring the need for effective diagnostic markers.MethodsWe 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.ResultsWe 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.ConclusionThis research highlights DCT, PMEL, and KIT as diagnostic biomarkers for DFUs, which are linked to melanin production and the MAPK/PI3K-Akt signaling pathways.https://www.frontiersin.org/articles/10.3389/fgene.2025.1620749/fulldiabetic foot ulcersWGCNAPPI networkmelanin synthesisdiagnosis
spellingShingle Yingnan Li
Ning Xiao
Zhuoqun Wang
Wenhai Wang
Fengjiao Li
Jiren Wang
An analysis of gene expression profiles through machine learning uncovers the new diagnostic signature for diabetic foot ulcers
Frontiers in Genetics
diabetic foot ulcers
WGCNA
PPI network
melanin synthesis
diagnosis
title An analysis of gene expression profiles through machine learning uncovers the new diagnostic signature for diabetic foot ulcers
title_full An analysis of gene expression profiles through machine learning uncovers the new diagnostic signature for diabetic foot ulcers
title_fullStr An analysis of gene expression profiles through machine learning uncovers the new diagnostic signature for diabetic foot ulcers
title_full_unstemmed An analysis of gene expression profiles through machine learning uncovers the new diagnostic signature for diabetic foot ulcers
title_short An analysis of gene expression profiles through machine learning uncovers the new diagnostic signature for diabetic foot ulcers
title_sort analysis of gene expression profiles through machine learning uncovers the new diagnostic signature for diabetic foot ulcers
topic diabetic foot ulcers
WGCNA
PPI network
melanin synthesis
diagnosis
url https://www.frontiersin.org/articles/10.3389/fgene.2025.1620749/full
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