Establishment Of Omics Detection Method And Marker Screening For Hyperuricemia Based On Mass Spectrometry

Objective: Establishment of proteomic and metabolomic detection methods for hyperuricemia based on mass spectrometry and screening of its characteristic omics markers.Methods: MB-WCX was used to remove high-abundance proteins in the plasma samples of the research subjects,and then combined with matrix-assisted laser desorption ionization time-of-flight mass spectrometry（MALDI-TOF MS）technology for detection to obtain plasma polypeptide/protein profiles of patients with hyperuricemia,construct their mass spectrometry diagnostic models and optimize the detection methodology.Non-labeled quantitative detection of the above-mentioned specimens was carried out by nano-liquid chromatography quadrupole time-of-flight mass spectrometry（nano-LC-Q-TOF MS/MS）technology,and the proteomic characteristic markers of the hyperuricemia group were screened and analyzed,GO analysis and KEGG analysis were performed to understand its biological function.Plasma metabolomic analysis of hyperuricemia using ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry（UHPLC-Q-TOF-MS）technology to screen its metabolomic signature markers and analyze its associated metabolic pathways.Results:（1）Based on MALDI-TOF MS,a plasma polypeptide/protein diagnosis prediction model for hyperuricemia was established.The recognition ability of the model was 98.02%,and the cross-validation was 87.74%.The model was verified by the validation group,and the sensitivity was 73.30%,the specificity was 60.00%.（2）A total of 13 differential proteins were identified in hyperuricemia,including 6 upregulated proteins and 7 down-regulated proteins.Functional enrichment analysis found that most of the differential proteins functioned outside the cell.KEGG analysis showed that the process of cholesterol metabolism was closely related to hyperuricemia.（3）A total of 24 differential metabolites were screened by plasma metabolomic analysis.ROC curve analysis showed that there were 7 metabolites except uric acid with AUC >0.75,which could be used as new markers for predicting and diagnosing hyperuricemia.Pathway analysis indicated that phenylpropanoid Amino acid,tyrosine and tryptophan biosynthesis and glycerophospholipid metabolism pathways are closely related to hyperuricemia.Conclusion: Established a hyperuricemia plasma diagnosis prediction model based on MALDI-TOF MS technology,which provides an important reference for clinical diagnosis of early hyperuricemia;Established hyperuricemia plasma proteomics and metabolomic detection methods to screen out the omics markers and metabolic pathways closely related to hyperuricemia,providing a basis for the mechanism study of hyperuricemia.