Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, China.
Front Immunol. 2024 Feb 22;15:1329009. doi: 10.3389/fimmu.2024.1329009. eCollection 2024.
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.
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.
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.
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.
系统性红斑狼疮（SLE）患者肾脏损害最常见的原因是狼疮肾炎（LN），LN 也是发病率和死亡率的重要危险因素。乳酸代谢和蛋白质乳酰化可能与 LN 的发生有关。然而，目前还缺乏相关研究来验证这一假说。因此，本研究旨在筛选 LN 的乳酸相关生物标志物，并分析其潜在机制。
为了在训练集（GSE32591、GSE127797）中识别差异表达基因（DEGs），我们进行了 LN 样本与正常样本之间的差异表达分析。然后，我们使用 WGCNA 针对 LN 挖掘模块基因。通过 DEGs、关键模块基因和乳酸相关基因（LRGs）的重叠，创建乳酸相关差异表达基因（LR-DEGs）。通过使用机器学习算法、ROC 和表达水平，发现了生物标志物。我们还根据生物标志物和 GSEA 进行了免疫浸润研究。
LN 组与正常组之间获得了 1259 个 DEGs。然后，获得了与 LN 相关的 3800 个模块基因。通过 DEGs、关键模块基因和 LRGs 的交集，筛选出 19 个 LR-DEGs。此外，通过两种机器学习算法获得了 8 个关键基因。随后，获得了与乳酸代谢相关的 3 个生物标志物，包括 COQ2、COQ4 和 NDUFV1。这三个生物标志物在通路“抗原加工和呈递”和“NOD 样受体信号通路”中富集。我们发现这三个生物标志物与巨噬细胞 M0 和调节性 T 细胞（Tregs）有关。
总之，研究结果表明，与乳酸相关的生物标志物 COQ2、COQ4 和 NDUFV1 与 LN 有关，为 LN 的诊断和治疗奠定了理论基础。
