Comprehensive Analysis of Lactate-related Gene Profiles and Immune Characteristics in Lupus Nephritis

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 Mar 8

PMID 38455045

Authors

Zhan Sun

Zhanyan Gao

Mengmeng Xiang

Yang Feng

Jie Wang

Jinhua Xu

Yilun Wang

Jun Liang

Affiliations

Soon will be listed here.

Abstract

Objectives: The most frequent cause of kidney damage in systemic lupus erythematosus (SLE) is lupus nephritis (LN), which is also a significant risk factor for morbidity and mortality. Lactate metabolism and protein lactylation might be related to the development of LN. However, there is still a lack of relative research to prove the hypothesis. Hence, this study was conducted to screen the lactate-related biomarkers for LN and analyze the underlying mechanism.

Methods: To identify differentially expressed genes (DEGs) in the training set (GSE32591, GSE127797), we conducted a differential expression analysis (LN samples versus normal samples). Then, module genes were mined using WGCNA concerning LN. The overlapping of DEGs, critical module genes, and lactate-related genes (LRGs) was used to create the lactate-related differentially expressed genes (LR-DEGs). By using a machine-learning algorithm, ROC, and expression levels, biomarkers were discovered. We also carried out an immune infiltration study based on biomarkers and GSEA.

Results: A sum of 1259 DEGs was obtained between LN and normal groups. Then, 3800 module genes in reference to LN were procured. 19 LR-DEGs were screened out by the intersection of DEGs, key module genes, and LRGs. Moreover, 8 pivotal genes were acquired via two machine-learning algorithms. Subsequently, 3 biomarkers related to lactate metabolism were obtained, including COQ2, COQ4, and NDUFV1. And these three biomarkers were enriched in pathways 'antigen processing and presentation' and 'NOD-like receptor signaling pathway'. We found that Macrophages M0 and T cells regulatory (Tregs) were associated with these three biomarkers as well.

Conclusion: Overall, the results indicated that lactate-related biomarkers COQ2, COQ4, and NDUFV1 were associated with LN, which laid a theoretical foundation for the diagnosis and treatment of LN.

Citing Articles

Lactate metabolism and lactylation in kidney diseases: insights into mechanisms and therapeutic opportunities.

Cheng Y, Guo L Ren Fail. 2025; 47(1):2469746.

PMID: 40012230 PMC: 11869332. DOI: 10.1080/0886022X.2025.2469746.

Lactylation in health and disease: physiological or pathological?.

Zhao L, Qi H, Lv H, Liu W, Zhang R, Yang A Theranostics. 2025; 15(5):1787-1821.

PMID: 39897556 PMC: 11780532. DOI: 10.7150/thno.105353.

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