Matrix metalloproteinase 14 and plasma kallikrein 1 may be potential biomarkers in the diagnosis and treatment of sepsis: a proteomics and bioinformatics analysis / 中华危重病急救医学

ABSTRACT

Objective:To analyze protein profiles in septic patients, and to find potential new targets for the diagnosis and treatment of sepsis.Methods:A cross sectional observational study was conducted. From January to December 2019, 12 septic patients and 9 healthy volunteers were recruited in the emergency intensive care unit (EICU) of the emergency department of the Affiliated Hospital of Southwest Medical University. The peripheral blood of the two groups was collected for protein mass spectrometry analysis, and the data-independent acquisition technology was used to obtain the expression data of each protein. The obtained data was imported into the online network tool Integrated Differential Expression and Pathway analysis (IDEP2), the data underwent ID converted and were homogenized to verify their comparability, and then principal component analysis was used to eliminate outlier data. Then data with P < 0.05, log 2fold change (FC) > 1 or log 2FC < -1 were considered to have a statistically significant difference, and the differential proteins were screened out. On the DAVID website, the screened differential proteins would be analyzed by gene ontology (GO), and the biological process, cellular components, and molecular function of the proteins would be analyzed. Protein enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Protein-protein interaction (PPI) analysis was performed through the Search Tool for the Retrieval of Interacting Genes Database (STRING) website to find closely related proteins. Results:The data in this study were shown to be comparable after normalization. A total of 125 differential proteins were screened, of which 99 were up-regulated and 26 were down-regulated. GO enrichment analysis discovered that these proteins were mainly extracellular, with cellular regulatory functions and catalytic functions involved in biological regulation, metabolic process and immune process. KEGG pathway analysis suggested that these proteins were involved in amino acid, carbohydrate metabolism and immune-related pathways. PPI analysis showed that key proteins included matrix metalloproteinase 14 (MMP14), fibulin 1 (FBLN1), plasma kallikrein 1 (KLKB1), etc., and finally screened out MMP14 and KLKB1, which were closely related to inflammation and immunity. Both might be potential new targets for early diagnosis and treatment of sepsis.Conclusion:MMP14 and KLKB1 may be potential biomarkers for the diagnosis, treatment and prognosis of sepsis.