Analysis of m6A-regulated genes and subtype classification in lupus nephritis

Abstract Background Lupus nephritis (LN) is the most common and severe clinical manifestation of systemic lupus erythematosus (SLE). N6-methyladenosine (m6A) is a reversible RNA modification and has been implicated in various biological processes. However, the roles of m6A regulators in LN are not f...

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Main Authors: Diangeng Li, Yanchun Li, Kaiyi Zhu, Yuqing Yuan, Zheng He, Qianmei Sun, Meiling Jin
Format: Article
Language:English
Published: BMC 2024-04-01
Series:BMC Nephrology
Subjects:
Online Access:https://doi.org/10.1186/s12882-024-03549-3
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author Diangeng Li
Yanchun Li
Kaiyi Zhu
Yuqing Yuan
Zheng He
Qianmei Sun
Meiling Jin
author_facet Diangeng Li
Yanchun Li
Kaiyi Zhu
Yuqing Yuan
Zheng He
Qianmei Sun
Meiling Jin
author_sort Diangeng Li
collection DOAJ
description Abstract Background Lupus nephritis (LN) is the most common and severe clinical manifestation of systemic lupus erythematosus (SLE). N6-methyladenosine (m6A) is a reversible RNA modification and has been implicated in various biological processes. However, the roles of m6A regulators in LN are not fully demonstrated. Methods We downloaded the kidney tissue transcriptome dataset of LN patients and normal controls from the GEO database and extracted the expression levels of m6A regulators. We constructed and compared Random Forest (RF) and Support Vector Machine (SVM) models, and subsequently selected featured genes to develop nomogram models. The m6A subtypes were identified based on significantly differentially expressed m6A regulators, and the m6A gene subtypes were identified based on m6A-associated differential genes, and the two m6A modification patterns were comprehensively evaluated. Results We obtained the GSE32591 and GSE112943 datasets from the GEO database, including 78 LN samples and 36 normal control samples. We extracted the expression levels of 20 m6A regulators. By RF analysis we identified 7 characteristic m6A regulators and constructed nomogramh models with these 7 genes. We identified two m6A subtypes based on these seven important m6A regulators, and the immune cell infiltration levels of the two subtype clusters were significantly different. We identified two more m6A gene subtypes based on m6A-associated DEGs. We calculated the m6A scores using the principal component analysis (PCA) algorithm and found that the m6A scores of m6A cluster A and gene cluster A were lower than those of m6A cluster B and gene cluster B. In addition, we found that the levels of inflammatory factors were also significantly different between m6A clusters and gene clusters. Conclusion This study confirms that m6A regulators are involved in the LN process through different modes of action and provide new diagnostic and therapeutic targets for LN.
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spelling doaj.art-8741582ad4d241fc878c31e68be20c2c2024-04-07T11:11:29ZengBMCBMC Nephrology1471-23692024-04-0125111110.1186/s12882-024-03549-3Analysis of m6A-regulated genes and subtype classification in lupus nephritisDiangeng Li0Yanchun Li1Kaiyi Zhu2Yuqing Yuan3Zheng He4Qianmei Sun5Meiling Jin6Department of Nephrology, Beijing-Chaoyang Hospital, Capital Medical UniversityDepartment of Nephrology, Beijing-Chaoyang Hospital, Capital Medical UniversityDepartment of Nephrology, Beijing-Chaoyang Hospital, Capital Medical UniversityDepartment of Nephrology, Beijing-Chaoyang Hospital, Capital Medical UniversityDepartment of Clinical Laboratory, Chinese PLA General HospitalDepartment of Nephrology, Beijing-Chaoyang Hospital, Capital Medical UniversityDepartment of Nephrology, Beijing-Chaoyang Hospital, Capital Medical UniversityAbstract Background Lupus nephritis (LN) is the most common and severe clinical manifestation of systemic lupus erythematosus (SLE). N6-methyladenosine (m6A) is a reversible RNA modification and has been implicated in various biological processes. However, the roles of m6A regulators in LN are not fully demonstrated. Methods We downloaded the kidney tissue transcriptome dataset of LN patients and normal controls from the GEO database and extracted the expression levels of m6A regulators. We constructed and compared Random Forest (RF) and Support Vector Machine (SVM) models, and subsequently selected featured genes to develop nomogram models. The m6A subtypes were identified based on significantly differentially expressed m6A regulators, and the m6A gene subtypes were identified based on m6A-associated differential genes, and the two m6A modification patterns were comprehensively evaluated. Results We obtained the GSE32591 and GSE112943 datasets from the GEO database, including 78 LN samples and 36 normal control samples. We extracted the expression levels of 20 m6A regulators. By RF analysis we identified 7 characteristic m6A regulators and constructed nomogramh models with these 7 genes. We identified two m6A subtypes based on these seven important m6A regulators, and the immune cell infiltration levels of the two subtype clusters were significantly different. We identified two more m6A gene subtypes based on m6A-associated DEGs. We calculated the m6A scores using the principal component analysis (PCA) algorithm and found that the m6A scores of m6A cluster A and gene cluster A were lower than those of m6A cluster B and gene cluster B. In addition, we found that the levels of inflammatory factors were also significantly different between m6A clusters and gene clusters. Conclusion This study confirms that m6A regulators are involved in the LN process through different modes of action and provide new diagnostic and therapeutic targets for LN.https://doi.org/10.1186/s12882-024-03549-3Lupus nephritism6A regulatorsBioinformatics analysisImmunoinfiltration
spellingShingle Diangeng Li
Yanchun Li
Kaiyi Zhu
Yuqing Yuan
Zheng He
Qianmei Sun
Meiling Jin
Analysis of m6A-regulated genes and subtype classification in lupus nephritis
BMC Nephrology
Lupus nephritis
m6A regulators
Bioinformatics analysis
Immunoinfiltration
title Analysis of m6A-regulated genes and subtype classification in lupus nephritis
title_full Analysis of m6A-regulated genes and subtype classification in lupus nephritis
title_fullStr Analysis of m6A-regulated genes and subtype classification in lupus nephritis
title_full_unstemmed Analysis of m6A-regulated genes and subtype classification in lupus nephritis
title_short Analysis of m6A-regulated genes and subtype classification in lupus nephritis
title_sort analysis of m6a regulated genes and subtype classification in lupus nephritis
topic Lupus nephritis
m6A regulators
Bioinformatics analysis
Immunoinfiltration
url https://doi.org/10.1186/s12882-024-03549-3
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