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Evaluation of Biomarkers and Immune Microenvironment of Osteoarthritis: Evidence From Omics Data and Machine Learning
Objectives: This study aimed to identify novel biomarkers for osteoarthritis (OA) and explore potential pathological immune cell infiltration. Methods: We identified differentially expressed genes (DEGs) between OA and normal synovial tissues using the limma package in R, and performed enrichment an...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149375/ https://www.ncbi.nlm.nih.gov/pubmed/35651940 http://dx.doi.org/10.3389/fgene.2022.905027 |
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author | Liu, Zhixin Liu, Heng Li, Deqiang Ma, Liang Lu, Tongxin Sun, Hao Zhang, Yuankai Yang, Hui |
author_facet | Liu, Zhixin Liu, Heng Li, Deqiang Ma, Liang Lu, Tongxin Sun, Hao Zhang, Yuankai Yang, Hui |
author_sort | Liu, Zhixin |
collection | PubMed |
description | Objectives: This study aimed to identify novel biomarkers for osteoarthritis (OA) and explore potential pathological immune cell infiltration. Methods: We identified differentially expressed genes (DEGs) between OA and normal synovial tissues using the limma package in R, and performed enrichment analyses to understand the functions and enriched pathways of DEGs. Weighted gene co-expression network analysis (WGCNA) and distinct machine-learning algorithms were then used to identify hub modules and candidate biomarkers. We assessed the diagnostic value of the candidate biomarkers using receiver operating characteristic (ROC) analysis. We then used the CIBERSORT algorithm to analyze immune cell infiltration patterns, and the Wilcoxon test to screen out hub immune cells that might affect OA occurrence. Finally, the expression levels of hub biomarkers were confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: We identified 102 up-regulated genes and 110 down-regulated genes. The functional enrichment analysis results showed that DEGs are enriched mainly in immune response pathways. Combining the results of the algorithms and ROC analysis, we identified GUCA1A and NELL1 as potential diagnostic biomarkers for OA, and validated their diagnosibility using an external dataset. Construction of a TF-mRNA-miRNA network enabled prediction of potential candidate compounds targeting hub biomarkers. Immune cell infiltration analyses revealed the expression of hub biomarkers to be correlated with CD8 T cells, memory B cells, M0/M2 macrophages, resting mast cells and resting dendritic cells. qRT-PCR results showed both GUCA1A and NELL1 were significantly increased in OA samples (p < 0.01). All validations are consistent with the microarray hybridization, indicating that GUCA1A and NELL1 may be involved in the pathogenesis of OA. Conclusion: The findings suggest that GUCA1A and NELL1, closely related to OA occurrence and progression, represent new OA candidate markers, and that immune cell infiltration plays a significant role in the progression of OA. |
format | Online Article Text |
id | pubmed-9149375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91493752022-05-31 Evaluation of Biomarkers and Immune Microenvironment of Osteoarthritis: Evidence From Omics Data and Machine Learning Liu, Zhixin Liu, Heng Li, Deqiang Ma, Liang Lu, Tongxin Sun, Hao Zhang, Yuankai Yang, Hui Front Genet Genetics Objectives: This study aimed to identify novel biomarkers for osteoarthritis (OA) and explore potential pathological immune cell infiltration. Methods: We identified differentially expressed genes (DEGs) between OA and normal synovial tissues using the limma package in R, and performed enrichment analyses to understand the functions and enriched pathways of DEGs. Weighted gene co-expression network analysis (WGCNA) and distinct machine-learning algorithms were then used to identify hub modules and candidate biomarkers. We assessed the diagnostic value of the candidate biomarkers using receiver operating characteristic (ROC) analysis. We then used the CIBERSORT algorithm to analyze immune cell infiltration patterns, and the Wilcoxon test to screen out hub immune cells that might affect OA occurrence. Finally, the expression levels of hub biomarkers were confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: We identified 102 up-regulated genes and 110 down-regulated genes. The functional enrichment analysis results showed that DEGs are enriched mainly in immune response pathways. Combining the results of the algorithms and ROC analysis, we identified GUCA1A and NELL1 as potential diagnostic biomarkers for OA, and validated their diagnosibility using an external dataset. Construction of a TF-mRNA-miRNA network enabled prediction of potential candidate compounds targeting hub biomarkers. Immune cell infiltration analyses revealed the expression of hub biomarkers to be correlated with CD8 T cells, memory B cells, M0/M2 macrophages, resting mast cells and resting dendritic cells. qRT-PCR results showed both GUCA1A and NELL1 were significantly increased in OA samples (p < 0.01). All validations are consistent with the microarray hybridization, indicating that GUCA1A and NELL1 may be involved in the pathogenesis of OA. Conclusion: The findings suggest that GUCA1A and NELL1, closely related to OA occurrence and progression, represent new OA candidate markers, and that immune cell infiltration plays a significant role in the progression of OA. Frontiers Media S.A. 2022-05-16 /pmc/articles/PMC9149375/ /pubmed/35651940 http://dx.doi.org/10.3389/fgene.2022.905027 Text en Copyright © 2022 Liu, Liu, Li, Ma, Lu, Sun, Zhang and Yang. 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 | Genetics Liu, Zhixin Liu, Heng Li, Deqiang Ma, Liang Lu, Tongxin Sun, Hao Zhang, Yuankai Yang, Hui Evaluation of Biomarkers and Immune Microenvironment of Osteoarthritis: Evidence From Omics Data and Machine Learning |
title | Evaluation of Biomarkers and Immune Microenvironment of Osteoarthritis: Evidence From Omics Data and Machine Learning |
title_full | Evaluation of Biomarkers and Immune Microenvironment of Osteoarthritis: Evidence From Omics Data and Machine Learning |
title_fullStr | Evaluation of Biomarkers and Immune Microenvironment of Osteoarthritis: Evidence From Omics Data and Machine Learning |
title_full_unstemmed | Evaluation of Biomarkers and Immune Microenvironment of Osteoarthritis: Evidence From Omics Data and Machine Learning |
title_short | Evaluation of Biomarkers and Immune Microenvironment of Osteoarthritis: Evidence From Omics Data and Machine Learning |
title_sort | evaluation of biomarkers and immune microenvironment of osteoarthritis: evidence from omics data and machine learning |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9149375/ https://www.ncbi.nlm.nih.gov/pubmed/35651940 http://dx.doi.org/10.3389/fgene.2022.905027 |
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