| Objective:Clinical data of patients with Parkinson’s Disease(PD)and Health Control(HC)were collected,and the content of clinically degraded monosaccharides was detected.By comparing intrinsic differences in serum degraded monosaccharide levels between patients with Parkinson’s disease and healthy controls as well as between patients with Parkinson’s disease at various stages,we explore and analyze the value of glycomic-based biomarkers in assisting diagnosis and evaluation of Parkinson’s disease.Methods:A retrospective case-control study was used in this study.Serum samples were collected from 109 patients with Parkinson’s disease admitted to West Coast Hospital,Affiliated Hospital of Qingdao University from June 2018 to March 2022,as well as from healthy people undergoing physical examination.According to the exclusion criteria,serum samples of 86 patients with Parkinson’s disease were included in the study.According to the age-sex matching method,86 patients who underwent physical examination in the Health Center of the Affiliated Hospital of Qingdao University were matched as the control group.A total of 86 patients with PD were randomly divided into 2 groups at a ratio of 7:3:the training set cohort(60 PD,60 HC)and the internal validation set cohort(26 PD,26HC).High performance liquid chromatography(HPLC)was used to determine the content of degraded monosaccharides in serum and to quantitatively analyze their constituents.The receiver operating characteristic(ROC)and area under the curve(AUC)were used to evaluate the diagnostic efficacy of different monosaccharides in the pathological behavior of Parkinson’s disease,combined with the univariate analysis of clinical test indicators with significant differences in each cohort.Multivariate Logistic regression was used to construct the auxiliary diagnosis Model-PD for Parkinson’s disease.Model-PD was evaluated by likelihood ratio test and C index,and ROC curve was used to test the Model.Model-PD is verified in internal validation set.Visualizing and Calibration of Model-PD by Nomogram.Parkinson’s disease patients were divided into early and middle and late groups according to their H-Y grades.The changes of serum degraded monosaccharides and clinical indicators between the two groups were compared and verified in the internal verification set,and the trend of the changes of each indicator in the two sets was observed.Results:1.In the degraded serum monosaccharides composition of Parkinson’s disease group and healthy control group,a total of 6 monosaccharides including glucosamine(Glc N),galactose amino(Gal N),mannose(Man),glucose(Glc),galactose(Gal)and fucose(Fuc)were included for analysis.In the two sets,the content of mannose and fucose in PD group was lower than that in control group,while the content of galactose in PD group was higher than that in control group,and the difference was statistically significant.Area under the curve(AUC)of Man,Gal and Fuc alone as diagnostic markers for Parkinson’s disease were0.746,0.622 and 0.676,respectively.2.In the comparison of clinical metabolism between Parkinson’s disease and healthy control group,four clinical indicators including creatinine,glucose,triglyceride and calcium ion were included for unifactor analysis.Among them,the contents of glucose,triglyceride and calcium ion in the two sets were lower in PD group than in the control group,and the difference in results was statistically significant.3.Based on the differences in clinical indicators and monosaccharide content between the Parkinson’s disease group and the healthy control group,the Logistic regression was used to analyze and build the diagnosis Model of PD,namely the combination of glucose,triglyceride,calcium ion,Man,Gal and Fuc,and it was found that the model could well distinguish the patients with Parkinson’s disease from the healthy physical examination population.The AUC was 0.972,the sensitivity was 96.296%,the specificity was 89.655%and the accuracy was 92.857%.4.Model evaluation was carried out on the established Parkinson’s disease diagnostic model Model-PD.Model test and differentiation evaluation were respectively used,and it was found that the model was generally meaningful and had a high degree of accuracy.5.Model-PD was verified in the internal verification set,and it was found that its AUC was 0.920,sensitivity was 88.462%,specificity was 88.462%,and accuracy was88.462%..6.The analysis of various indicators in different H-Y stages of Parkinson’s disease showed that triglycerides in advanced patients in the training set were significantly lower than those in early patients,while creatinine levels in middle and advanced patients were significantly higher than those in early patients,and the same trend was observed in the internal validation set.Conclusion:The "sugar fingerprint" characteristics of degraded monosaccharides in serum of PD patients and PD patients were different from those of healthy people.Among them,the distribution of Man,Gal and Fuc is different between PD group and HC group.Compared with HC group,the content of Man and Fuc in serum of PD group is lower,while the content of Gal is higher.Univariate analysis of clinical indicators showed that the content of glucose,triglyceride and calcium ion in PD group was significantly lower than that in HC group.The diagnostic model based on serum monosaccharides and clinical indicators showed good diagnostic efficacy in distinguishing Parkinson’s disease patients from healthy people,and had certain reference significance and auxiliary diagnostic help for clinical diagnosis and evaluation.The changes of monosaccharide components and clinical indicators are also different in different stages of the patient population,which is a promising clinical biomarker. |
PDF Full Text Request