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Among them, GPX1, RCN1, and UBE2D3 exhibited high diagnostic value (AUC &gt; 0.7, p &lt; 0.05), and the diagnostic potential of GPX1 and RCN1 was confirmed in the animal model. The study found that memory B cells, plasma cells, neutrophils, and M1 macrophages were significantly increased in MS patients, while naive B cells and activated NK cells decreased. Consensus clustering based on key ERS-related genes divided MS patients into two subtypes. Single-cell sequencing showed that microglia and pericytes were the cell types with the highest expression of key ERS-related genes, and the APP-CD74 pathway was enhanced in the brain tissue of MS patients. Mendelian randomization analysis suggested that GPX1 plays a protective role in MS. These findings reveal the mechanisms of ERS-related biomarkers in MS and provide potential targets for diagnosis and treatment.<\/jats:p>","DOI":"10.3390\/ijms26136286","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:56:54Z","timestamp":1751353014000},"page":"6286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["GPX1 and RCN1 as New Endoplasmic Reticulum Stress-Related Biomarkers in Multiple Sclerosis Brain Tissue and Their Involvement in the APP-CD74 Pathway: An Integrated Study Combining Machine Learning and Multi-Omics"],"prefix":"10.3390","volume":"26","author":[{"given":"Zhixin","family":"Qiao","sequence":"first","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"},{"name":"The Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China, Harbin Medical University, Ministry of Education, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"},{"name":"The Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China, Harbin Medical University, Ministry of Education, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoru","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xiu","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujuan","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xijun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, 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