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
Abstract
1. Introduction
2. Result
2.1. Identification of DEGs Between Brain Tissues of Multiple Sclerosis Patients and Controls
2.2. Identification and Validation of Key ERS-DEGs
2.3. Immune Infiltration Analysis in MS
2.4. Unsupervised Clustering and Analysis of MS
2.5. Expression of Key ERS-DEGs in Single-Cell Data
2.6. Analysis of Cell Communication in MS
2.7. Conducting Separate Analyses of Cell Communication via the APP-CD74 Pathway in MS and the EAE Mouse Model
2.8. Functional Roles of Microglia and Pericytes via the APP-CD74 Pathway in MS
2.9. MR Analysis Between Key ERS-DEGs and MS
3. Discussion
4. Materials and Methods
4.1. Data Acquisition
4.2. Weighted Gene Co-Expression Network Analysis
4.3. Identification of Differentially Expressed Genes (DEGs)
4.4. Identification and Validation of ERS-DEGs Associated with Clinical Traits in MS
4.5. Immune Infiltration Analysis in Multiple Sclerosis Using CIBERSORT
4.6. Subclustering Analysis Using Key ERS-DEGs
4.7. Processing and Clustering of Single-Nucleus RNA and Single-Cell RNA Data
4.8. Scoring of Key ERS-DEGs in snRNA-seq
4.9. Cell Communication Analysis
4.10. Collection of GWAS Data and Two-Sample Mendelian Randomization Analysis
4.11. Immunohistochemistry and Immunofluorescence
4.12. Establishment of EAE Model
4.13. RNA Extraction and qRT-PCR
4.14. Flow Cytometry Analysis
4.15. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Qiao, Z.; Wang, Y.; Ma, X.; Zhang, X.; Wu, J.; Li, A.; Wang, C.; Xiu, X.; Zhang, S.; Lang, X.; et al. 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. Int. J. Mol. Sci. 2025, 26, 6286. https://doi.org/10.3390/ijms26136286
Qiao Z, Wang Y, Ma X, Zhang X, Wu J, Li A, Wang C, Xiu X, Zhang S, Lang X, et al. 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. International Journal of Molecular Sciences. 2025; 26(13):6286. https://doi.org/10.3390/ijms26136286
Chicago/Turabian StyleQiao, Zhixin, Yanping Wang, Xiaoru Ma, Xiyu Zhang, Junfeng Wu, Anqi Li, Chao Wang, Xin Xiu, Sifan Zhang, Xiujuan Lang, and et al. 2025. "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" International Journal of Molecular Sciences 26, no. 13: 6286. https://doi.org/10.3390/ijms26136286
APA StyleQiao, Z., Wang, Y., Ma, X., Zhang, X., Wu, J., Li, A., Wang, C., Xiu, X., Zhang, S., Lang, X., Liu, X., Sun, B., Li, H., & Liu, Y. (2025). 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. International Journal of Molecular Sciences, 26(13), 6286. https://doi.org/10.3390/ijms26136286