Abstract
Sepsis is defined as an organ dysfunction syndrome and it has high mortality worldwide. This study analysed the proteome of serum from patients with sepsis to characterize the pathological mechanism and pathways involved in sepsis. A total of 59 patients with sepsis were enrolled for quantitative proteomic analysis. Weighted gene co-expression network analysis (WGCNA) was performed to construct a co-expression network specific to sepsis. Key regulatory modules that were detected were highly correlated with sepsis patients and related to multiple functional groups, including plasma lipoprotein particle remodeling, inflammatory response, and wound healing. Complement activation was significantly associated with sepsis-associated encephalopathy. Triglyceride/cholesterol homeostasis was found to be related to sepsis-associated acute kidney injury. Twelve hub proteins were identified, which might be predictive biomarkers of sepsis. External validation of the hub proteins showed their significantly differential expression in sepsis patients. This study identified that plasma lipoprotein processes played a crucial role in sepsis patients, that complement activation contributed to sepsis-associated encephalopathy, and that triglyceride/cholesterol homeostasis was associated with sepsis-associated acute kidney injury.
Highlights
Sepsis is a lethal condition defined as an organ dysfunction syndrome caused by an uncontrolled inflammatory response to infection
Patients and clinical characteristics A total of 114 patients with sepsis and 62 healthy normal controls (NCs) were enrolled in this study, 90 of whom were placed in the derivation group (59 patients with sepsis and 31 NC), and the remaining subjects were included in the validation group (Fig 1)
The levels of laboratory indices, including white blood cell count, haemoglobin level, haematocrit, platelet count, albumin level, aspartate aminotransferase level, and creatinine level, were significantly worse in the sepsis patients compared to the NC group
Summary
Sepsis is a lethal condition defined as an organ dysfunction syndrome caused by an uncontrolled inflammatory response to infection. Several studies have used proteomic analysis to investigate specific biomarkers regulating the pathogenic mechanism of sepsis (Nguyen & Yaffe, 2003; Middleton et al, 2019; Seymour et al, 2019). These studies were performed by differential proteomic analysis followed by enrichment analyses to establish functional pathways and were based on common laboratory indicators or low-throughput techniques. Identification of co-expression patterns might provide in-depth knowledge into sepsis-associated biological pathways
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