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Prioritization of Diagnostic and Prognostic Biomarkers for Lupus Nephritis Based on Integrated Bioinformatics Analyses

Lupus nephritis (LN) is an important driver of end-stage renal disease (ESRD). However, few biomarkers are available for evaluating the diagnosis and prognosis of LN. For this study, we downloaded microarray data of multiple LN expression profiles from the GEO database. We used the WGCNA and R limma...

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Autores principales: Chen, Zhimin, Lan, Ruilong, Ye, Keng, Chen, Hong, Chen, Caiming, Xu, Yanfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531593/
https://www.ncbi.nlm.nih.gov/pubmed/34692653
http://dx.doi.org/10.3389/fbioe.2021.717234
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author Chen, Zhimin
Lan, Ruilong
Ye, Keng
Chen, Hong
Chen, Caiming
Xu, Yanfang
author_facet Chen, Zhimin
Lan, Ruilong
Ye, Keng
Chen, Hong
Chen, Caiming
Xu, Yanfang
author_sort Chen, Zhimin
collection PubMed
description Lupus nephritis (LN) is an important driver of end-stage renal disease (ESRD). However, few biomarkers are available for evaluating the diagnosis and prognosis of LN. For this study, we downloaded microarray data of multiple LN expression profiles from the GEO database. We used the WGCNA and R limma packages to identify LN hub genes and differentially-expressed genes (DEGs). We identified nine co-DEGs in the intersection with LN-related genes from the Genecards database. We found DEGs that are primarily associated with immune-related functions and pathways (including with the complement pathway, primary immunodeficiency markers, and MHC-like protein complexes) through our comprehensive GSEA, GO, and KEGG enrichment analyses. We used other LN and SLE validation datasets and discovered six explicitly expressed co-DEGs: HLA-DMA, HLA-DPA1, HLA-DPB1, HLA-DRA, IL10RA, and IRF8 in the LN set; ROC and Precision-Recall curve analyses revealed that these six genes have a good diagnostic efficacy. The correlation analysis with prognostic data from the Nephroseq database indicates that the differential expression of these co-DEGs is associated with a low glomerular filtration rate in that cohort. Additionally, we used a single-cell LN database of immune cells (for the first time) and discovered these co-DEGs to be predominantly distributed in different types of macrophages and B cells. In conclusion, by integrating multiple approaches for DEGs discovery, we identified six valuable biomarkers that are strongly correlated with the diagnosis and prognosis of LN. These markers can help clarify the pathogenesis and improve the clinical management of LN.
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spelling pubmed-85315932021-10-23 Prioritization of Diagnostic and Prognostic Biomarkers for Lupus Nephritis Based on Integrated Bioinformatics Analyses Chen, Zhimin Lan, Ruilong Ye, Keng Chen, Hong Chen, Caiming Xu, Yanfang Front Bioeng Biotechnol Bioengineering and Biotechnology Lupus nephritis (LN) is an important driver of end-stage renal disease (ESRD). However, few biomarkers are available for evaluating the diagnosis and prognosis of LN. For this study, we downloaded microarray data of multiple LN expression profiles from the GEO database. We used the WGCNA and R limma packages to identify LN hub genes and differentially-expressed genes (DEGs). We identified nine co-DEGs in the intersection with LN-related genes from the Genecards database. We found DEGs that are primarily associated with immune-related functions and pathways (including with the complement pathway, primary immunodeficiency markers, and MHC-like protein complexes) through our comprehensive GSEA, GO, and KEGG enrichment analyses. We used other LN and SLE validation datasets and discovered six explicitly expressed co-DEGs: HLA-DMA, HLA-DPA1, HLA-DPB1, HLA-DRA, IL10RA, and IRF8 in the LN set; ROC and Precision-Recall curve analyses revealed that these six genes have a good diagnostic efficacy. The correlation analysis with prognostic data from the Nephroseq database indicates that the differential expression of these co-DEGs is associated with a low glomerular filtration rate in that cohort. Additionally, we used a single-cell LN database of immune cells (for the first time) and discovered these co-DEGs to be predominantly distributed in different types of macrophages and B cells. In conclusion, by integrating multiple approaches for DEGs discovery, we identified six valuable biomarkers that are strongly correlated with the diagnosis and prognosis of LN. These markers can help clarify the pathogenesis and improve the clinical management of LN. Frontiers Media S.A. 2021-10-08 /pmc/articles/PMC8531593/ /pubmed/34692653 http://dx.doi.org/10.3389/fbioe.2021.717234 Text en Copyright © 2021 Chen, Lan, Ye, Chen, Chen and Xu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Chen, Zhimin
Lan, Ruilong
Ye, Keng
Chen, Hong
Chen, Caiming
Xu, Yanfang
Prioritization of Diagnostic and Prognostic Biomarkers for Lupus Nephritis Based on Integrated Bioinformatics Analyses
title Prioritization of Diagnostic and Prognostic Biomarkers for Lupus Nephritis Based on Integrated Bioinformatics Analyses
title_full Prioritization of Diagnostic and Prognostic Biomarkers for Lupus Nephritis Based on Integrated Bioinformatics Analyses
title_fullStr Prioritization of Diagnostic and Prognostic Biomarkers for Lupus Nephritis Based on Integrated Bioinformatics Analyses
title_full_unstemmed Prioritization of Diagnostic and Prognostic Biomarkers for Lupus Nephritis Based on Integrated Bioinformatics Analyses
title_short Prioritization of Diagnostic and Prognostic Biomarkers for Lupus Nephritis Based on Integrated Bioinformatics Analyses
title_sort prioritization of diagnostic and prognostic biomarkers for lupus nephritis based on integrated bioinformatics analyses
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531593/
https://www.ncbi.nlm.nih.gov/pubmed/34692653
http://dx.doi.org/10.3389/fbioe.2021.717234
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