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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Introduction
Lupus nephritis (LN) is one of the most common and serious complications of systemic lupus erythematosus (SLE) with high morbidity and mortality rates [1]. The global annual incidence of SLE ranges from 1/100,000 to 8.7/100,000, and 40-60% of patients with SLE have LN at the time of onset. approximately 10-20% of patients with LN will eventually develop end-stage renal disease (ESRD) [2]. The treatment of LN is mainly based on glucocorticoids and immunosuppressive agents, but the therapeutic effect is not satisfactory [ The original datasets were downloaded from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/). The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request. 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This study is supported by Bei**g Hospitals Authority Youth Program (No. QML 20220306 and No. QML 20210303), and Bei**g Association for Science and Technology **qiao Project Seed Fund (Grant No. ZZ22006). MJ and DL analyzed the data and drafted the manuscript. YL, YY, ZH and KZ designed the study, analyzed the data, and revised the manuscript. QS designed and conducted the study, analyzed the data, and drafted and revised the manuscript. All authors contribute to this work and gave final approval of the manuscript. Not applicable. Not applicable. The authors declare no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Below is the link to the electronic supplementary material. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Li, D., Li, Y., Zhu, K. et al. Analysis of m6A-regulated genes and subtype classification in lupus nephritis.
BMC Nephrol 25, 119 (2024). https://doi.org/10.1186/s12882-024-03549-3 Received: Accepted: Published: DOI: https://doi.org/10.1186/s12882-024-03549-3Data availability
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