| Background:Wilson’s disease(WD),also known as Hepatolenticular degeneration(HLD),is an autosomal recessive genetic disease caused by abnormal copper deposition caused by ATP7 B gene mutation and corresponding organ damage.The clinical manifestations are complex and diverse,the age span is wide,the onset of the disease is different,and the disease continues to progress,which can lead to progressive disability and death.At present,WD diagnostic scores mainly include serum ceruloplasmin,24-hour urinary copper,K-F ring,liver copper,and gene mutation detection.However,when ceruloplasmin level,24-hour urine copper,liver copper staining and genetic testing do not show typical changes,it makes the diagnosis more difficult and easy to miss and misdiagnose.Therefore,it is particularly important to find more sensitive and specific markers for the diagnosis of this disease.The early pathological changes of WD are steatosis,which is similar to nonalcoholic fatty liver disease,but the specific mechanism of lipid changes is not clear.In addition,the proteome and metabolome are directly related to each other because protein levels can affect the metabolic profile of a cellular system and metabolite concentrations may affect protein expression.The study of single omics can only reflect the changes of diseases at one level,which has certain limitations.Therefore,the combined analysis of proteomics and lipid metabolomics is needed to explore the pathogenesis of WD,find potential specific biomarkers,and achieve early diagnosis and treatment of WD.Aims:The purpose of this study is to apply the lipid metabolomics and proteomics tools based on mass spectrometry to explore the potential relationship between differential metabolites and differential proteins,explore the pathogenesis of the disease,find potential markers of WD,and provide a basis for the diagnosis of WD.Methods:(1)In this study,18 WD patients and 75 healthy people diagnosed in the First Hospital of Jilin University were selected as the subjects,and they were divided into two groups: one group was called the patient group(P),and the other group was the control group(C).Early morning fasting blood samples were collected and pretreated in both groups.Finally,the P/C differentially expressed proteins and differential metabolites were obtained by using mass spectrometry-based lipid metabolomics and quantitative proteomics technology,respectively.(2)KEGG and Wiki pathway databases were used for enrichment analysis of the differentially expressed metabolites and proteins.(3)The regulatory network of proteins and metabolic small molecules was constructed based on KEGG reaction database,and the regulatory networks related to differential proteins and differential metabolites were extracted from the network.(4)Quantitative correlation analysis between proteins and metabolites was constructed to evaluate the regulatory relationship between proteins and metabolites.Finally,enrichment analysis was performed on the proteins and metabolism of the potential regulatory relationships obtained by screening.Results:1.There were 31 differential metabolites between the patient group and the control group,of which 15 metabolites were up-regulated,mainly belonging to triglycerides,diacylglycerides,phosphatidylcholine,phosphatidylinositol,sphingolipids,and a small part belonging to plant sphingosine and sphingosine.Sixteen down-regulated metabolites were found,mainly belonging to lysophosphatidylcholine and diacylglycerides,and a few belonged to ceramides,glycosphingolipids,cholesteryl esters and sphingomyelin.2.There were 246 differentially expressed proteins between the patient group and the control group,of which 119 proteins were up-regulated.127 proteins were downregulated.3.The differentially expressed proteins and differential metabolites between the patient group and the control group had potential regulatory relationships.The main affected lipid metabolism pathways were sphingolipid metabolism pathway,glycerophospholipid metabolism pathway and cholesterol metabolism pathway.4.Lecithin cholesterol acyltransferase(LCAT)was significantly down-regulated and phosphatidylcholine(PC)was significantly up-regulated in WD.Conclusions:1.Lipid metabolomic and proteomic studies have shown that there are significant changes in lipid metabolic pathways in patients with hepatolenticular degeneration.2.Lecithin cholesterol acyltransferase and phosphatidylcholine are related to the pathogenesis of hepatolenticular degeneration. |
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