Abstract
ObjectivesSepsis is the major cause of death for critically ill patients. Recent progress in proteomics permits a thorough characterization of the mechanisms associated with critical illness. The purpose of this study was to screen potential biomarkers for early prognostic assessment of patients with sepsis.MethodsFor the discovery stage, 30 sepsis patients with different prognoses were selected. Urinary proteins were identified using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with LC-MS/MS. Mass spec instrument analysis were performed with Mascot software and the International Protein Index (IPI); bioinformatic analyses were used by the algorithm of set and the Gene Ontology (GO) Database. For the verification stage, the study involved another 54 sepsis-hospitalized patients, with equal numbers of patients in survivor and non-survivor groups based on 28-day survival. Differentially expressed proteins were verified by Western Blot.ResultsA total of 232 unique proteins were identified. Proteins that were differentially expressed were further analyzed based on the pathophysiology of sepsis and biomathematics. For sepsis prognosis, five proteins were significantly up-regulated: selenium binding protein-1, heparan sulfate proteoglycan-2, alpha-1-B glycoprotein, haptoglobin, and lipocalin; two proteins were significantly down-regulated: lysosome-associated membrane proteins-1 and dipeptidyl peptidase-4. Based on gene ontology clustering, these proteins were associated with the biological processes of lipid homeostasis, cartilage development, iron ion transport, and certain metabolic processes. Urinary LAMP-1 was down-regulated, consistent with the Western Blot validation.ConclusionThis study provides the proteomic analysis of urine to identify prognostic biomarkers of sepsis. The seven identified proteins provide insight into the mechanism of sepsis. Low urinary LAMP-1 levels may be useful for early prognostic assessment of sepsis.Trial RegistrationClinicalTrial.gov NCT01493492
Highlights
Sepsis is a challenge to the field of critical care medicine
If sepsis is not controlled in time, lasting and excessive inflammation can stimulate the progression of moderate sepsis to severe sepsis or even multiple organ dysfunction (MOD) [3]
Recruitment of Subjects Subjects were selected from inpatients who were hospitalized between May 2010 and Oct 2011 in the Respiratory intensive care unit (ICU), Surgical ICU, and Emergency ICU at Chinese People’s Liberation Army (PLA) General Hospital
Summary
Sepsis is a challenge to the field of critical care medicine. In the United States alone, 751,000 new patients suffer from severe sepsis annually, resulting in 210,000 deaths [1]. Nonspecific clinical manifestations, complicating its diagnosis and the assessment of its severity and prognosis [2]. If sepsis is not controlled in time, lasting and excessive inflammation can stimulate the progression of moderate sepsis to severe sepsis or even multiple organ dysfunction (MOD) [3]. Sepsis-associated MOD is one of the main causes of death of intensive care unit (ICU) patients. The prognosis of sepsis must be assessed as early as possible
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