Cellular senescence-associated genes in rheumatoid arthritis: Identification and functional analysis.
Rheumatoid arthritis (RA), a long-term autoinflammatory condition causing joint damage and deformities, involves a multifaceted pathogenesis with genetic, epigenetic, and immune factors, including early immune aging. However, its precise cause remains elusive. Cellular senescence, a hallmark of agin...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0317364 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832540294665469952 |
|---|---|
| author | You Ao Qing Lan Tianhua Yu Zhichao Wang Jing Zhang |
| author_facet | You Ao Qing Lan Tianhua Yu Zhichao Wang Jing Zhang |
| author_sort | You Ao |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA), a long-term autoinflammatory condition causing joint damage and deformities, involves a multifaceted pathogenesis with genetic, epigenetic, and immune factors, including early immune aging. However, its precise cause remains elusive. Cellular senescence, a hallmark of aging marked by a permanent halt in cell division due to damage and stress, is crucial in aging and related diseases. In our study, we analyzed RA microarray data from the Gene Expression Omnibus (GEO) and focused on cellular senescence genes from the CellAge database. We started by selecting five RA datasets from GEO. Next, we pinpointed 29 differentially expressed genes (DEGs) linked to cellular senescence in RA, aligning them with genes from CellAge. We explored the roles of these DEGs in cellular senescence through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. We then pinpointed three key genes (DHX9, CYR61, and ITGB) using random forest and LASSO Cox regression machine learning techniques. An integrated diagnostic model was created using these genes. We also examined the variance in immune cell infiltration and immune checkpoint gene expression between RA and normal samples. Our methodology's predictive accuracy was confirmed in external validation cohorts. Subsequently, RA samples were classified into three distinct subgroups based on the cellular senescence-associated DEGs, and we compared their immune landscapes. Our findings reveal a significant impact of cellular senescence-related DEGs on immune cell infiltration in RA samples. Hence, a deeper understanding of cellular senescence in RA could offer new perspectives for diagnosis and treatment. |
| format | Article |
| id | doaj-art-f739d4402e35449ebf95e99046a48162 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-f739d4402e35449ebf95e99046a481622025-02-05T05:31:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031736410.1371/journal.pone.0317364Cellular senescence-associated genes in rheumatoid arthritis: Identification and functional analysis.You AoQing LanTianhua YuZhichao WangJing ZhangRheumatoid arthritis (RA), a long-term autoinflammatory condition causing joint damage and deformities, involves a multifaceted pathogenesis with genetic, epigenetic, and immune factors, including early immune aging. However, its precise cause remains elusive. Cellular senescence, a hallmark of aging marked by a permanent halt in cell division due to damage and stress, is crucial in aging and related diseases. In our study, we analyzed RA microarray data from the Gene Expression Omnibus (GEO) and focused on cellular senescence genes from the CellAge database. We started by selecting five RA datasets from GEO. Next, we pinpointed 29 differentially expressed genes (DEGs) linked to cellular senescence in RA, aligning them with genes from CellAge. We explored the roles of these DEGs in cellular senescence through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. We then pinpointed three key genes (DHX9, CYR61, and ITGB) using random forest and LASSO Cox regression machine learning techniques. An integrated diagnostic model was created using these genes. We also examined the variance in immune cell infiltration and immune checkpoint gene expression between RA and normal samples. Our methodology's predictive accuracy was confirmed in external validation cohorts. Subsequently, RA samples were classified into three distinct subgroups based on the cellular senescence-associated DEGs, and we compared their immune landscapes. Our findings reveal a significant impact of cellular senescence-related DEGs on immune cell infiltration in RA samples. Hence, a deeper understanding of cellular senescence in RA could offer new perspectives for diagnosis and treatment.https://doi.org/10.1371/journal.pone.0317364 |
| spellingShingle | You Ao Qing Lan Tianhua Yu Zhichao Wang Jing Zhang Cellular senescence-associated genes in rheumatoid arthritis: Identification and functional analysis. PLoS ONE |
| title | Cellular senescence-associated genes in rheumatoid arthritis: Identification and functional analysis. |
| title_full | Cellular senescence-associated genes in rheumatoid arthritis: Identification and functional analysis. |
| title_fullStr | Cellular senescence-associated genes in rheumatoid arthritis: Identification and functional analysis. |
| title_full_unstemmed | Cellular senescence-associated genes in rheumatoid arthritis: Identification and functional analysis. |
| title_short | Cellular senescence-associated genes in rheumatoid arthritis: Identification and functional analysis. |
| title_sort | cellular senescence associated genes in rheumatoid arthritis identification and functional analysis |
| url | https://doi.org/10.1371/journal.pone.0317364 |
| work_keys_str_mv | AT youao cellularsenescenceassociatedgenesinrheumatoidarthritisidentificationandfunctionalanalysis AT qinglan cellularsenescenceassociatedgenesinrheumatoidarthritisidentificationandfunctionalanalysis AT tianhuayu cellularsenescenceassociatedgenesinrheumatoidarthritisidentificationandfunctionalanalysis AT zhichaowang cellularsenescenceassociatedgenesinrheumatoidarthritisidentificationandfunctionalanalysis AT jingzhang cellularsenescenceassociatedgenesinrheumatoidarthritisidentificationandfunctionalanalysis |