Identification of potential biomarkers and mechanisms for keloid disorder based on comprehensive bioinformatics analysis and machine learning algorithms

Abstract Background Keloid disorder (KD) encompasses a spectrum of fibroproliferative dermal conditions, the pathogenesis remains complex and incompletely understood. This study sought to identify biomarkers and potential therapeutic targets for KD through an integrative bioinformatics approach and...

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Main Authors: Bowen Zheng, Jianxiong Qiao, Xiaoping Yu, Hanghang Zhou, Anqi Wang, Xuanfen Zhang
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Medical Genomics
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Online Access:https://doi.org/10.1186/s12920-025-02174-9
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author Bowen Zheng
Jianxiong Qiao
Xiaoping Yu
Hanghang Zhou
Anqi Wang
Xuanfen Zhang
author_facet Bowen Zheng
Jianxiong Qiao
Xiaoping Yu
Hanghang Zhou
Anqi Wang
Xuanfen Zhang
author_sort Bowen Zheng
collection DOAJ
description Abstract Background Keloid disorder (KD) encompasses a spectrum of fibroproliferative dermal conditions, the pathogenesis remains complex and incompletely understood. This study sought to identify biomarkers and potential therapeutic targets for KD through an integrative bioinformatics approach and machine learning analysis of RNA sequencing data. Methods RNA sequencing was performed on skin tissue samples from 13 patients with KD and 14 healthy controls. Using weighted gene co-expression network analysis and differential expression analysis revealed differentially expressed key module genes, and the CytoHubba plugin identified candidate genes. Subsequently analyzed using least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) methods to pinpoint feature genes associated with KD. Following this, biomarkers were determined through expression level validation, enrichment analysis, and immune infiltration analysis. Results A total of 420 differentially expressed key module genes were identified, and the top 10 genes with DMNC values were selected as candidate genes. Five feature genes were selected through LASSO and SVM-RFE, with NID2, MFAP2, COL8A1, and P4HA3 showing significant expression differences between KD and control samples, along with consistent expression patterns across datasets, identified as potential biomarkers. These four biomarkers were proved to possess high diagnostic potential, and they were found to exhibit significant positive correlations with one another. Functional enrichment analysis indicated that the primary KEGG pathways associated with these biomarkers included “steroid hormone biosynthesis” and “cytokine–cytokine receptor interaction.” Moreover, immune infiltration analysis revealed that the four biomarkers were negatively correlated with type 17 T helper cells and positively correlated with 15 immune cell types, including activated B cells and central memory CD4 T cells. Conclusion In conclusion, NID2, MFAP2, COL8A1, and P4HA3 were identified as key biomarkers for KD, offering new avenues for more targeted and effective diagnostic and therapeutic strategies for managing this condition.
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spelling doaj-art-2eaedbfaa07244b1883767717dbf18b92025-08-20T03:04:15ZengBMCBMC Medical Genomics1755-87942025-07-0118111810.1186/s12920-025-02174-9Identification of potential biomarkers and mechanisms for keloid disorder based on comprehensive bioinformatics analysis and machine learning algorithmsBowen Zheng0Jianxiong Qiao1Xiaoping Yu2Hanghang Zhou3Anqi Wang4Xuanfen Zhang5Department of Plastic Surgery, The Second Hospital & Clinical Medical School, Lanzhou UniversityDepartment of Plastic Surgery, The Second Hospital & Clinical Medical School, Lanzhou UniversityThe Department of Burn, Gansu Provincial HospitalDepartment of Plastic Surgery, The Second Hospital & Clinical Medical School, Lanzhou UniversityNHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial HospitalDepartment of Plastic Surgery, The Second Hospital & Clinical Medical School, Lanzhou UniversityAbstract Background Keloid disorder (KD) encompasses a spectrum of fibroproliferative dermal conditions, the pathogenesis remains complex and incompletely understood. This study sought to identify biomarkers and potential therapeutic targets for KD through an integrative bioinformatics approach and machine learning analysis of RNA sequencing data. Methods RNA sequencing was performed on skin tissue samples from 13 patients with KD and 14 healthy controls. Using weighted gene co-expression network analysis and differential expression analysis revealed differentially expressed key module genes, and the CytoHubba plugin identified candidate genes. Subsequently analyzed using least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) methods to pinpoint feature genes associated with KD. Following this, biomarkers were determined through expression level validation, enrichment analysis, and immune infiltration analysis. Results A total of 420 differentially expressed key module genes were identified, and the top 10 genes with DMNC values were selected as candidate genes. Five feature genes were selected through LASSO and SVM-RFE, with NID2, MFAP2, COL8A1, and P4HA3 showing significant expression differences between KD and control samples, along with consistent expression patterns across datasets, identified as potential biomarkers. These four biomarkers were proved to possess high diagnostic potential, and they were found to exhibit significant positive correlations with one another. Functional enrichment analysis indicated that the primary KEGG pathways associated with these biomarkers included “steroid hormone biosynthesis” and “cytokine–cytokine receptor interaction.” Moreover, immune infiltration analysis revealed that the four biomarkers were negatively correlated with type 17 T helper cells and positively correlated with 15 immune cell types, including activated B cells and central memory CD4 T cells. Conclusion In conclusion, NID2, MFAP2, COL8A1, and P4HA3 were identified as key biomarkers for KD, offering new avenues for more targeted and effective diagnostic and therapeutic strategies for managing this condition.https://doi.org/10.1186/s12920-025-02174-9Keloid disorderBiomarkerMolecular mechanismsBioinformatics
spellingShingle Bowen Zheng
Jianxiong Qiao
Xiaoping Yu
Hanghang Zhou
Anqi Wang
Xuanfen Zhang
Identification of potential biomarkers and mechanisms for keloid disorder based on comprehensive bioinformatics analysis and machine learning algorithms
BMC Medical Genomics
Keloid disorder
Biomarker
Molecular mechanisms
Bioinformatics
title Identification of potential biomarkers and mechanisms for keloid disorder based on comprehensive bioinformatics analysis and machine learning algorithms
title_full Identification of potential biomarkers and mechanisms for keloid disorder based on comprehensive bioinformatics analysis and machine learning algorithms
title_fullStr Identification of potential biomarkers and mechanisms for keloid disorder based on comprehensive bioinformatics analysis and machine learning algorithms
title_full_unstemmed Identification of potential biomarkers and mechanisms for keloid disorder based on comprehensive bioinformatics analysis and machine learning algorithms
title_short Identification of potential biomarkers and mechanisms for keloid disorder based on comprehensive bioinformatics analysis and machine learning algorithms
title_sort identification of potential biomarkers and mechanisms for keloid disorder based on comprehensive bioinformatics analysis and machine learning algorithms
topic Keloid disorder
Biomarker
Molecular mechanisms
Bioinformatics
url https://doi.org/10.1186/s12920-025-02174-9
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