Comprehensive analysis of lactate-related gene profiles and immune characteristics in lupus nephritis

Zhan Sun; Zhanyan Gao; Mengmeng Xiang; Yang Feng; Jie Wang; Jinhua Xu; Yilun Wang; Jun Liang

doi:10.3389/fimmu.2024.1329009

Comprehensive analysis of lactate-related gene profiles and immune characteristics in lupus nephritis

Front Immunol. 2024 Feb 22:15:1329009. doi: 10.3389/fimmu.2024.1329009. eCollection 2024.

Authors

Zhan Sun¹, Zhanyan Gao¹, Mengmeng Xiang¹, Yang Feng¹, Jie Wang¹, Jinhua Xu², Yilun Wang¹, Jun Liang¹

Affiliations

¹ Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
² Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, China.

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.

Keywords: GEO; bioinformatics; infiltrating immunocytes; lactate; lupus nephritis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Humans
Lactic Acid
Lupus Erythematosus, Systemic*
Lupus Nephritis*
Signal Transduction

Substances

Lactic Acid
Biomarkers

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (No. 82073443, 81872526), Shanghai Municipal Commission of Health and Family Planning (No. 2023ZZ02018), Shanghai Municipal Key Clinical Specialty (No. shslczdzk01002).