Identification of Biomarkers Co-Associated with Lactylation and Acetylation in Systemic Lupus Erythematosus

<b>Background:</b> Systemic lupus erythematosus (SLE) is an immune-mediated disease with widespread involvement, and its pathogenesis remains incompletely understood. Recent studies suggest that modifications such as acetylation and lactylation play crucial roles in SLE progression, with...

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Main Authors: Zhanyan Gao, Yang Feng, Chenghui Zheng, Fei Li, Zhan Sun, Mengmeng Xiang, Junrong Zhu, Mingyu Chu, Jinhua Xu, Jun Liang
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/6/1274
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author Zhanyan Gao
Yang Feng
Chenghui Zheng
Fei Li
Zhan Sun
Mengmeng Xiang
Junrong Zhu
Mingyu Chu
Jinhua Xu
Jun Liang
author_facet Zhanyan Gao
Yang Feng
Chenghui Zheng
Fei Li
Zhan Sun
Mengmeng Xiang
Junrong Zhu
Mingyu Chu
Jinhua Xu
Jun Liang
author_sort Zhanyan Gao
collection DOAJ
description <b>Background:</b> Systemic lupus erythematosus (SLE) is an immune-mediated disease with widespread involvement, and its pathogenesis remains incompletely understood. Recent studies suggest that modifications such as acetylation and lactylation play crucial roles in SLE progression, with potential interrelationships between them. This study aimed to identify biomarker genes co-associated with both lactylation and acetylation and to explore their potential mechanisms in SLE pathogenesis. <b>Methods:</b> Microarray data from peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database. In the training dataset (GSE81622), differential expression analysis was performed to compare SLE samples with healthy controls. Lactate- and acetylation-related genes were used to identify differentially expressed lactate-related genes (LR-DEGs) and acetylation-related genes (AR-DEGs). Genes co-associated with both lactylation and acetylation were further examined. LASSO regression, support vector machine recursive feature elimination (SVM-RFE), and ROC curve analysis were used to identify hub genes. Immune infiltration analysis and a clinical nomogram model were developed for accurate diagnosis and treatment prediction. qPCR was used to validate the hub genes. <b>Results:</b> A total of 1181 differentially expressed genes (DEGs) were identified between SLE and healthy groups. Of these, 33 LR-DEGs and 28 AR-DEGs were identified. Seven genes were found to be co-associated with both lactylation and acetylation. Using LASSO and SVM-RFE, two hub genes, CDCA5 and MCTS1, were identified and validated in the GSE24706 dataset. ROC curve analysis and clinical nomogram revealed significant associations of these biomarkers with SLE pathogenesis. <b>Conclusions:</b> Our study identifies CDCA5 and MCTS1 as potential biomarkers for SLE, potentially influencing its pathogenesis through histone lactylation and acetylation. Experimental validation confirmed their differential expression between SLE patients and healthy controls. These findings underscore the role of epigenetic modifications in SLE, offering new insights into its regulatory mechanisms and immune interactions.
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spelling doaj-art-ee6e636262c14cd5ba55a6bb932cbe002025-08-20T02:24:31ZengMDPI AGBiomedicines2227-90592025-05-01136127410.3390/biomedicines13061274Identification of Biomarkers Co-Associated with Lactylation and Acetylation in Systemic Lupus ErythematosusZhanyan Gao0Yang Feng1Chenghui Zheng2Fei Li3Zhan Sun4Mengmeng Xiang5Junrong Zhu6Mingyu Chu7Jinhua Xu8Jun Liang9Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Dermatology, Shanghai Institute of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China<b>Background:</b> Systemic lupus erythematosus (SLE) is an immune-mediated disease with widespread involvement, and its pathogenesis remains incompletely understood. Recent studies suggest that modifications such as acetylation and lactylation play crucial roles in SLE progression, with potential interrelationships between them. This study aimed to identify biomarker genes co-associated with both lactylation and acetylation and to explore their potential mechanisms in SLE pathogenesis. <b>Methods:</b> Microarray data from peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database. In the training dataset (GSE81622), differential expression analysis was performed to compare SLE samples with healthy controls. Lactate- and acetylation-related genes were used to identify differentially expressed lactate-related genes (LR-DEGs) and acetylation-related genes (AR-DEGs). Genes co-associated with both lactylation and acetylation were further examined. LASSO regression, support vector machine recursive feature elimination (SVM-RFE), and ROC curve analysis were used to identify hub genes. Immune infiltration analysis and a clinical nomogram model were developed for accurate diagnosis and treatment prediction. qPCR was used to validate the hub genes. <b>Results:</b> A total of 1181 differentially expressed genes (DEGs) were identified between SLE and healthy groups. Of these, 33 LR-DEGs and 28 AR-DEGs were identified. Seven genes were found to be co-associated with both lactylation and acetylation. Using LASSO and SVM-RFE, two hub genes, CDCA5 and MCTS1, were identified and validated in the GSE24706 dataset. ROC curve analysis and clinical nomogram revealed significant associations of these biomarkers with SLE pathogenesis. <b>Conclusions:</b> Our study identifies CDCA5 and MCTS1 as potential biomarkers for SLE, potentially influencing its pathogenesis through histone lactylation and acetylation. Experimental validation confirmed their differential expression between SLE patients and healthy controls. These findings underscore the role of epigenetic modifications in SLE, offering new insights into its regulatory mechanisms and immune interactions.https://www.mdpi.com/2227-9059/13/6/1274lactylationacetylationsystemic lupus erythematosusCDCA5MCTS1
spellingShingle Zhanyan Gao
Yang Feng
Chenghui Zheng
Fei Li
Zhan Sun
Mengmeng Xiang
Junrong Zhu
Mingyu Chu
Jinhua Xu
Jun Liang
Identification of Biomarkers Co-Associated with Lactylation and Acetylation in Systemic Lupus Erythematosus
Biomedicines
lactylation
acetylation
systemic lupus erythematosus
CDCA5
MCTS1
title Identification of Biomarkers Co-Associated with Lactylation and Acetylation in Systemic Lupus Erythematosus
title_full Identification of Biomarkers Co-Associated with Lactylation and Acetylation in Systemic Lupus Erythematosus
title_fullStr Identification of Biomarkers Co-Associated with Lactylation and Acetylation in Systemic Lupus Erythematosus
title_full_unstemmed Identification of Biomarkers Co-Associated with Lactylation and Acetylation in Systemic Lupus Erythematosus
title_short Identification of Biomarkers Co-Associated with Lactylation and Acetylation in Systemic Lupus Erythematosus
title_sort identification of biomarkers co associated with lactylation and acetylation in systemic lupus erythematosus
topic lactylation
acetylation
systemic lupus erythematosus
CDCA5
MCTS1
url https://www.mdpi.com/2227-9059/13/6/1274
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