鉴定膜性肾病中与免疫和炎症相关的生物标志物：全面的生物信息学分析和验证。
Identification of biomarkers related to immune and inflammation in membranous nephropathy: comprehensive bioinformatic analysis and validation.
机构信息
Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.
Renal Research Institution of Beijing University of Chinese Medicine, and Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
出版信息
Front Immunol. 2023 Oct 9;14:1252347. doi: 10.3389/fimmu.2023.1252347. eCollection 2023.
BACKGROUND
Membranous nephropathy (MN) is an autoimmune glomerular disease that is predominantly mediated by immune complex deposition and complement activation. The aim of this study was to identify key biomarkers of MN and investigate their association with immune-related mechanisms, inflammatory cytokines, chemokines and chemokine receptors (CCRs).
METHODS
MN cohort microarray expression data were downloaded from the GEO database. Differentially expressed genes (DEGs) in MN were identified, and hub genes were determined using a protein-protein interaction (PPI) network. The relationships between immune-related hub genes, immune cells, CCRs, and inflammatory cytokines were examined using immune infiltration analysis, gene set enrichment analysis (GSEA), and weighted gene co-expression network analysis (WGCNA). Finally, the immune-related hub genes in MN were validated using ELISA.
RESULTS
In total, 501 DEGs were identified. Enrichment analysis revealed the involvement of immune- and cytokine-related pathways in MN progression. Using WGCNA and immune infiltration analysis, 2 immune-related hub genes ( and ) were identified. These genes exhibited significant correlations with a wide range of immune cells and were found to participate in B cell/T cell receptor and chemokine signaling pathways. In addition, the expressions of 2 immune-related hub genes were positively correlated with the expression of , , , , , and .
CONCLUSION
Our study identified and as immune-related hub genes that potentially influence the expression of CCRs and pro-inflammatory cytokines (, , , , , and ). and may be potential biomarkers for MN progression, providing a perspective for diagnostic and immunotherapeutic targets of MN.
背景
膜性肾病（MN）是一种主要由免疫复合物沉积和补体激活介导的自身免疫性肾小球疾病。本研究旨在鉴定 MN 的关键生物标志物，并研究它们与免疫相关机制、炎症细胞因子、趋化因子和趋化因子受体（CCRs）的关联。
方法
从 GEO 数据库中下载 MN 队列微阵列表达数据。使用蛋白质-蛋白质相互作用（PPI）网络鉴定 MN 中的差异表达基因（DEGs），并确定关键基因。使用免疫浸润分析、基因集富集分析（GSEA）和加权基因共表达网络分析（WGCNA）研究免疫相关关键基因、免疫细胞、CCRs 和炎症细胞因子之间的关系。最后，使用 ELISA 验证 MN 中的免疫相关关键基因。
结果
共鉴定出 501 个 DEGs。富集分析显示，免疫和细胞因子相关途径参与了 MN 的进展。使用 WGCNA 和免疫浸润分析，鉴定出 2 个免疫相关关键基因（和）。这些基因与广泛的免疫细胞具有显著相关性，并被发现参与 B 细胞/T 细胞受体和趋化因子信号通路。此外，2 个免疫相关关键基因的表达与、、、、和的表达呈正相关。
结论
本研究鉴定出和作为免疫相关关键基因，它们可能影响 CCRs 和促炎细胞因子（、、、、和）的表达。和可能是 MN 进展的潜在生物标志物，为 MN 的诊断和免疫治疗靶点提供了新的视角。
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