Mortality-associated Plasma Proteome Dynamics in a Prospective Multicenter Sepsis Cohort
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ABSTRACT: Understanding the plasma proteome dynamics in sepsis patients is crucial for improving prognostic and therapeutic strategies, as sepsis remains a leading cause of mortality in intensive care units. In this study, 363 patients with newly diagnosed sepsis were enrolled and plasma was collected on the first and fourth day after diagnosis. Proteome analysis was performed using liquid chromatography–tandem mass spectrometry. The plasma proteome was analyzed via classical statistical analysis and machine learning to identify associations with 30-day survival. Out of 363 sepsis patients, 224 survived and 139 did not survive the 30-day period. Significant differences in the abundance of 87 proteins on day 1 and 95 proteins on day 4 were found between survivors and non-survivors. Additionally, between days 1 and 4, 63 proteins were differentially regulated between both groups. We found that protein regulations within the first days of sepsis were generally associated with a worse outcome. Statistical analysis revealed the underlying proteins to be foremost related to blood coagulation, immune response and complement activation. Complementarily, the machine learning classifier achieved an area under the receiver operating characteristic curve of 0.75 for predicting 30-day survival. The feature importance analysis highlighted additional proteins and substantiated the findings of univariate statistics. This study describes the temporal alterations of the plasma proteome and the underlying protein networks that are associated with survival. These findings enhance the understanding of sepsis pathophysiology and the identified proteins might serve as starting points for further investigations and guide the development of targeted therapeutic strategies.
INSTRUMENT(S): Orbitrap Fusion Lumos, Orbitrap Exploris 240
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Blood Plasma
DISEASE(S): Bacterial Sepsis,Covid-19
SUBMITTER: Thilo Bracht
LAB HEAD: Thilo Bracht
PROVIDER: PXD055932 | Pride | 2024-12-16
REPOSITORIES: Pride
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