Identification of biomarkers related to immune and inflammation in membranous nephropathy: comprehensive bioinformatic analysis and validation

Pingna Zhang; Yunling Geng; Jingyi Tang; Zijing Cao; Xiaojun Xiang; Kezhen Yang; Hongbo Chen

doi:10.3389/fimmu.2023.1252347

Identification of biomarkers related to immune and inflammation in membranous nephropathy: comprehensive bioinformatic analysis and validation

Front Immunol. 2023 Oct 9:14:1252347. doi: 10.3389/fimmu.2023.1252347. eCollection 2023.

Authors

Pingna Zhang¹, Yunling Geng², Jingyi Tang², Zijing Cao², Xiaojun Xiang¹, Kezhen Yang³, Hongbo Chen¹

Affiliations

¹ Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.
² 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.
³ Department of Rehabilitation Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Abstract

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 (CYBB and CSF1R) 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 CCR1, CX3CR1, IL1B, CCL4, TNF, and CCR2.

Conclusion: Our study identified CSF1 and CYBB as immune-related hub genes that potentially influence the expression of CCRs and pro-inflammatory cytokines (CCR1, CX3CR1, IL1B, CCL4, TNF, and CCR2). CSF1 and CYBB may be potential biomarkers for MN progression, providing a perspective for diagnostic and immunotherapeutic targets of MN.

Keywords: bioinformatics; biomarkers; immune; inflammatory cytokines; membranous nephropathy.

Publication types

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

MeSH terms

Autoimmune Diseases*
Biomarkers
Computational Biology
Cytokines / genetics
Glomerulonephritis, Membranous* / diagnosis
Glomerulonephritis, Membranous* / genetics
Humans
Inflammation / genetics

Substances

Biomarkers
Cytokines

Grants and funding

This study was supported by the Major project jointly constructed by the State Administration of Traditional Chinese Medicine and Zhejiang Provincial Administration of Traditional Chinese Medicine (GZY-ZJ-KJ-23013) and the Zhejiang natural science foundation of China (Y23H270009).