| Objective:Multiple sclerosis（MS）is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system（CNS）.The cause of multiple sclerosis is unknown,and there are currently no effective treatments to stop the progressive neurological disability.In the past few years,major advances in mass spectrometry instrumentation,proteomic methodologies,and bioinformatics have dramatically transformed neuroscience and multiple sclerosis.The proteomic workflow can reveal a large amount of proteomic data and has the ability to identify biomarkers,providing important functional and pathway information for multiple sclerosis diseases,and is a useful tool to meet the needs of multiple sclerosis research.However,at present,the discovery of MS biomarkers is mainly focused on the cerebrospinal fluid,and the research on the plasma proteome needs to be further strengthened.Methods:In this study,the researchers used the tandem mass spectrometry tagging（TMT）quantitative liquid chromatography-mass spectrometry proteomics（LC/MS）method to detect differentially expressed proteins（DEPs）in the plasma of 22 patients with multiple sclerosis and 22 healthy controls.)to check.Using data-independent acquisition（DDA）analysis of multiple sclerosis plasma proteomics quantified 375 proteins,using the criteria as follows: statistical P-value < 0.05,and proteins with a fold change（FC）> 1 were considered DEPs.Further bioinformatics analysis was performed on these DEPs,and the functional annotation of DEPs was analyzed using Gene Ontology（GO）and Innovation Pathway Analysis（IPA）.The candidate protein dipeptidyl peptidase IV（DPP4）was validated by enzyme-linked immunosorbent assay（ELISA）.Receiver operating characteristic（ROC）curves were used to determine the predictive potential of biomarkers.Finally,the researchers integrated the differential proteins of the previous study of multiple sclerosis blood proteome with the differential proteins of this study and compared it with the previous study of the multiple sclerosis cerebrospinal fluid proteome.Results:Among the 375 proteins quantified by LC/MS analysis,88 DEPs were identified among the 274 proteins quantified after deleting data with missing values greater than half of the total number of samples,of which 39 proteins were up-regulated and 49 were down-regulated.Comparing the results with similar studies in recent years,some of the48 proteins in this study（54%）overlapped with previous studies,with 40 newly identified proteins（46%）.This study is consistent with other studies,suggesting that the expression of multiple sclerosis proteins is relatively stable.The validated functions of DEPs were found to focus on binding and catalytic activities by gene ontology analysis,and further use of IPA analysis found that these DEPs proteins were involved in immune/inflammatory and neurological disease-related pathways.The area under the curve for the total protein consisting of HAUS augmin-like complex subunit 1（HAUS1）and Apolipoprotein L3（APOL3）was 0.994.A protein DPP4 related to multiple sclerosis treatment was verified by ELISA.Compared with the control group,the DPP4 protein in the multiple sclerosis group was significantly down-regulated,which was consistent with the results of mass spectrometry analysis.In addition,the functional pathway of plasma proteome DEPs in MS can reflect the pathology of MS.This part of the study shows that MS plasma proteomics is not only minimally invasive,relieves patient pain,can be collected continuously for early diagnosis and that biomarkers in MS plasma proteomics can better reflect the ability to predict multiple sclerosis Conclusion:1.Differentially expressed proteins（DEPs）related to multiple sclerosis can be found in the MS plasma proteome,and the HAUS1 and APOL3 proteins in plasma can be used as potential combined biomarkers with good prediction for MS disease.2.DPP4 in MS plasma is a down-regulated protein.3.The study of MS plasma proteomics suggests the potential molecular pathways of MS,which can provide help for clinical diagnosis and treatment. |
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