Precision Medicine Center, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Life Sci Alliance. 2021 Aug 24;4(10). doi: 10.26508/lsa.202101091. Print 2021 Oct.
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.
脓毒症定义为器官功能障碍综合征，在全球范围内具有很高的死亡率。本研究通过分析脓毒症患者的血清蛋白质组，以表征脓毒症涉及的病理机制和途径。共纳入 59 例脓毒症患者进行定量蛋白质组学分析。采用加权基因共表达网络分析（WGCNA）构建脓毒症特异性共表达网络。检测到的关键调控模块与脓毒症患者高度相关，并与多个功能群相关，包括血浆脂蛋白颗粒重塑、炎症反应和伤口愈合。补体激活与脓毒症相关性脑病显著相关。甘油三酯/胆固醇稳态与脓毒症相关性急性肾损伤有关。鉴定出 12 个枢纽蛋白，它们可能是脓毒症的预测生物标志物。枢纽蛋白的外部验证显示它们在脓毒症患者中的表达存在显著差异。本研究表明，血浆脂蛋白代谢在脓毒症患者中起着关键作用，补体激活有助于脓毒症相关性脑病，甘油三酯/胆固醇稳态与脓毒症相关性急性肾损伤有关。
