Characterization of a proteomic profile associated with organ dysfunction and mortality of sepsis and septic shock

Abstract

Introduction The search for new biomarkers that allow an early diagnosis in sepsis and predict its evolution has become a necessity in medicine. The objective of this study is to identify, through omics techniques, potential protein biomarkers that are expressed in patients with sepsis and their relationship with organ dysfunction and mortality. Methods Prospective, observational and single-center study that included adult patients (≥ 18 years) who were admitted to a tertiary hospital and who met the criteria for sepsis. A mass spectrometry-based approach was used to analyze the plasma proteins in the enrolled subjects. Subsequently, using recursive feature elimination classification and cross-validation with a vector classifier, an association of these proteins with mortality and organ dysfunction was established. The protein-protein interaction network was analyzed with String software. Results 141 patients were enrolled in this study. Mass spectrometry identified 177 proteins. Of all of them, and by recursive feature elimination, nine proteins (GPX3, APOB, ORM1, SERPINF1, LYZ, C8A, CD14, APOC3 and C1QC) were associated with organ dysfunction (SOFA > 6) with an accuracy of 0.82 ± 0.06, precision of 0.85 ± 0.093, sensitivity 0.81 ± 0.10, specificity 0.84 ± 0.10 and AUC 0.82 ± 0.06. Twenty-two proteins (CLU, LUM, APOL1, SAA1, CLEBC3B, C8A, ITIH4, KNG1, AGT, C7, SAA2, APOH, HRG, AFM, APOE, APOC1, C1S, SERPINC1, IGFALS, KLKB1, CFB and BTD) were associated with mortality with an accuracy of 0.86 ± 0.05, a precision of 0.91 ± 0.05, a sensitivity of 0.91 ± 0.05, a specificity of 0.72 ± 0.17, and an area under the curve (AUC) of 0.81 ± 0.08 with a confidence interval of 95%. Conclusion In sepsis there are proteomic patterns associated with organ dysfunction and mortality.

UMI-77 Modulates the Complement Cascade Pathway and Inhibits Inflammatory Factor Storm in Sepsis Based on TMT Proteomics and Inflammation Array Glass Chip

“…32,33 A proteomic study of 141 patients with sepsis indicated that serpinf1 was highly associated with organ dysfunction and Serpinc1 was highly associated with mortality. 34 Vtn was a key regulator of coagulation, serum VTN level was associated with sepsis-associated acute liver injury and pediatric intensive care unit (PICU) mortality, and VTN plus PRISM III was a powerful predictor of PICU mortality in pediatric patients with sepsis. 35 Fgb played a key role in coagulation and inflammation, which also associated with mortality and organ dysfunction of patients with sepsis.…”

“…The top 10 proteins within PPI network most associated with disease biology might be key drivers of UMI-77 in treatment of sepsis . Apoa2 and Apoa4 were important apoproteins, mainly involved in the synthesis of high-density lipoprotein, which could protect blood vessels and prevent atherosclerotic diseases such as cerebral thrombosis and coronary heart disease. , A proteomic study of 141 patients with sepsis indicated that serpinf1 was highly associated with organ dysfunction and Serpinc1 was highly associated with mortality . Vtn was a key regulator of coagulation, serum VTN level was associated with sepsis-associated acute liver injury and pediatric intensive care unit (PICU) mortality, and VTN plus PRISM III was a powerful predictor of PICU mortality in pediatric patients with sepsis .…”