Identification and Verification of Novel Biomarkers Involving Rheumatoid Arthritis with Multimachine Learning Algorithms: An In Silicon and In Vivo Study
Background. Rheumatoid arthritis (RA) remains one of the most prevalent chronic joint diseases. However, due to the heterogeneity among RA patients, there are still no robust diagnostic and therapeutic biomarkers for the diagnosis and treatment of RA. Methods. We retrieved RA-related and pan-cancer...
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| Format: | Article |
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Wiley
2024-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2024/3188216 |
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| author | Fucun Liu Juelan Ye Shouli Wang Yang Li Yuhang Yang Jianru Xiao Aimin Jiang Xuhua Lu Yunli Zhu |
| author_facet | Fucun Liu Juelan Ye Shouli Wang Yang Li Yuhang Yang Jianru Xiao Aimin Jiang Xuhua Lu Yunli Zhu |
| author_sort | Fucun Liu |
| collection | DOAJ |
| description | Background. Rheumatoid arthritis (RA) remains one of the most prevalent chronic joint diseases. However, due to the heterogeneity among RA patients, there are still no robust diagnostic and therapeutic biomarkers for the diagnosis and treatment of RA. Methods. We retrieved RA-related and pan-cancer information datasets from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. Six gene expression profiles and corresponding clinical information of GSE12021, GSE29746, GSE55235, GSE55457, GSE77298, and GSE89408 were adopted to perform differential expression gene analysis, enrichment, and immune component difference analyses of RA. Four machine learning algorithms, including LASSO, RF, XGBoost, and SVM, were used to identify RA-related biomarkers. Unsupervised cluster analysis was also used to decipher the heterogeneity of RA. A four-signature-based nomogram was constructed and verified to specifically diagnose RA and osteoarthritis (OA) from normal tissues. Consequently, RA-HFLS cell was utilized to investigate the biological role of CRTAM in RA. In addition, comparisons of diagnostic efficacy and biological roles among CRTAM and other classic biomarkers of RA were also performed. Results. Immune and stromal components were highly enriched in RA. Chemokine- and Th cell-related signatures were significantly activated in RA tissues. Four promising and novel biomarkers, including CRTAM, PTTG1IP, ITGB2, and MMP13, were identified and verified, which could be treated as novel treatment and diagnostic targets for RA. Nomograms based on the four signatures might aid in distinguishing and diagnosing RA, which reached a satisfactory performance in both training (AUC = 0.894) and testing (AUC = 0.843) cohorts. Two distinct subtypes of RA patients were identified, which further verified that these four signatures might be involved in the immune infiltration process. Furthermore, knockdown of CRTAM could significantly suppress the proliferation and invasion ability of RA cell line and thus could be treated as a novel therapeutic target. CRTAM owned a great diagnostic performance for RA than previous biomarkers including MMP3, S100A8, S100A9, IL6, COMP, LAG3, and ENTPD1. Mechanically, CRTAM could also be involved in the progression through immune dysfunction, fatty acid metabolism, and genomic instability across several cancer subtypes. Conclusion. CRTAM, PTTG1IP, ITGB2, and MMP13 were highly expressed in RA tissues and might function as pivotal diagnostic and treatment targets by deteriorating the immune dysfunction state. In addition, CRTAM might fuel cancer progression through immune signals, especially among RA patients. |
| format | Article |
| id | doaj-art-5a199d6035f74b3dbcec1136c242e7f4 |
| institution | Kabale University |
| issn | 1466-1861 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-5a199d6035f74b3dbcec1136c242e7f42025-02-03T01:29:32ZengWileyMediators of Inflammation1466-18612024-01-01202410.1155/2024/3188216Identification and Verification of Novel Biomarkers Involving Rheumatoid Arthritis with Multimachine Learning Algorithms: An In Silicon and In Vivo StudyFucun Liu0Juelan Ye1Shouli Wang2Yang Li3Yuhang Yang4Jianru Xiao5Aimin Jiang6Xuhua Lu7Yunli Zhu8Department of OrthopedicsWuxi School of MedicineOrthopedics Research CenterDepartment of OrthopedicsDepartment of OrthopedicsWuxi School of MedicineDepartment of UrologyDepartment of OrthopedicsDepartment of OrthopedicsBackground. Rheumatoid arthritis (RA) remains one of the most prevalent chronic joint diseases. However, due to the heterogeneity among RA patients, there are still no robust diagnostic and therapeutic biomarkers for the diagnosis and treatment of RA. Methods. We retrieved RA-related and pan-cancer information datasets from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. Six gene expression profiles and corresponding clinical information of GSE12021, GSE29746, GSE55235, GSE55457, GSE77298, and GSE89408 were adopted to perform differential expression gene analysis, enrichment, and immune component difference analyses of RA. Four machine learning algorithms, including LASSO, RF, XGBoost, and SVM, were used to identify RA-related biomarkers. Unsupervised cluster analysis was also used to decipher the heterogeneity of RA. A four-signature-based nomogram was constructed and verified to specifically diagnose RA and osteoarthritis (OA) from normal tissues. Consequently, RA-HFLS cell was utilized to investigate the biological role of CRTAM in RA. In addition, comparisons of diagnostic efficacy and biological roles among CRTAM and other classic biomarkers of RA were also performed. Results. Immune and stromal components were highly enriched in RA. Chemokine- and Th cell-related signatures were significantly activated in RA tissues. Four promising and novel biomarkers, including CRTAM, PTTG1IP, ITGB2, and MMP13, were identified and verified, which could be treated as novel treatment and diagnostic targets for RA. Nomograms based on the four signatures might aid in distinguishing and diagnosing RA, which reached a satisfactory performance in both training (AUC = 0.894) and testing (AUC = 0.843) cohorts. Two distinct subtypes of RA patients were identified, which further verified that these four signatures might be involved in the immune infiltration process. Furthermore, knockdown of CRTAM could significantly suppress the proliferation and invasion ability of RA cell line and thus could be treated as a novel therapeutic target. CRTAM owned a great diagnostic performance for RA than previous biomarkers including MMP3, S100A8, S100A9, IL6, COMP, LAG3, and ENTPD1. Mechanically, CRTAM could also be involved in the progression through immune dysfunction, fatty acid metabolism, and genomic instability across several cancer subtypes. Conclusion. CRTAM, PTTG1IP, ITGB2, and MMP13 were highly expressed in RA tissues and might function as pivotal diagnostic and treatment targets by deteriorating the immune dysfunction state. In addition, CRTAM might fuel cancer progression through immune signals, especially among RA patients.http://dx.doi.org/10.1155/2024/3188216 |
| spellingShingle | Fucun Liu Juelan Ye Shouli Wang Yang Li Yuhang Yang Jianru Xiao Aimin Jiang Xuhua Lu Yunli Zhu Identification and Verification of Novel Biomarkers Involving Rheumatoid Arthritis with Multimachine Learning Algorithms: An In Silicon and In Vivo Study Mediators of Inflammation |
| title | Identification and Verification of Novel Biomarkers Involving Rheumatoid Arthritis with Multimachine Learning Algorithms: An In Silicon and In Vivo Study |
| title_full | Identification and Verification of Novel Biomarkers Involving Rheumatoid Arthritis with Multimachine Learning Algorithms: An In Silicon and In Vivo Study |
| title_fullStr | Identification and Verification of Novel Biomarkers Involving Rheumatoid Arthritis with Multimachine Learning Algorithms: An In Silicon and In Vivo Study |
| title_full_unstemmed | Identification and Verification of Novel Biomarkers Involving Rheumatoid Arthritis with Multimachine Learning Algorithms: An In Silicon and In Vivo Study |
| title_short | Identification and Verification of Novel Biomarkers Involving Rheumatoid Arthritis with Multimachine Learning Algorithms: An In Silicon and In Vivo Study |
| title_sort | identification and verification of novel biomarkers involving rheumatoid arthritis with multimachine learning algorithms an in silicon and in vivo study |
| url | http://dx.doi.org/10.1155/2024/3188216 |
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