Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Felix-Hausdorff-Str. 8, 17475 Greifswald, Germany.
Jena University Hospital, Institute of Clinical Chemistry and Laboratory Diagnostics and Integrated Biobank Jena (IBBJ), Am Klinikum 1, 07740 Jena, Germany.
J Proteomics. 2020 Mar 1;214:103627. doi: 10.1016/j.jprot.2019.103627. Epub 2019 Dec 30.
A combined OMICS screening approach of human plasma and serum was used to characterize protein and metabolome signatures displaying association to severity of Community-acquired pneumonia (CAP). 240 serum and BD P100 EDTA plasma samples from patients diagnosed with CAP, collected during the day of enrolment to the hospital, were analyzed by a metabolomic and proteomic approach, respectively. Disease severity of CAP patients was stratified using the Sequential Organ Failure Assessment (SOFA) score. Quantitative proteome and metabolome data, derived by LC-MS/MS, were associated to SOFA and specific parameters of SOFA using linear regression models adjusted for age, BMI, sex, smoking and technical variables. Both proteome and metabolome profiling revealed remarkable strong changes in plasma and serum composition in relation to severity of CAP. Proteins and metabolites displaying SOFA associated levels are involved in immune response, particularly in processes of lipid metabolism. Proteins, which show an association to SOFA score, are involved in acute phase response, coagulation, complement activation and inflammation. Many of these metabolites and proteins displayed not only associations to SOFA, but also to parameters of SOFA score, which likely reflect the strong influence of lung-, liver-, kidney- and heart-dysfunction on the metabolome and proteome patterns. SIGNIFICANCE: Community-acquired pneumonia is the most frequent infection disease with high morbidity and mortality. So far, only few studies focused on the identification of proteins or metabolites associated to severity of CAP, often based on smaller sample sets. A screening for new diagnostic markers requires extensive sample collections in combination with high quality clinical data. To characterize the proteomic and metabolomics pattern associated to severity of CAP we performed a combined metabolomics and proteomic approach of serum and plasma sample from a multi-center clinical study focused on patients with CAP, requiring hospitalization. The results of this association study of omics data to the SOFA score enable not only an interpretation of changes in molecular patterns with severity of CAP but also an assignment of altered molecules to dysfunctions of respiratory, renal, coagulation, cardiovascular systems as well as liver.
采用 OMICS 联合筛选方法检测人血浆和血清，以鉴定与社区获得性肺炎（CAP）严重程度相关的蛋白质和代谢组学特征。对 240 例入院时确诊为 CAP 的患者血清和 EDTA 血浆样本进行代谢组学和蛋白质组学分析，分别采用 LC-MS/MS 获得定量蛋白质组学和代谢组学数据。采用序贯器官衰竭评估（SOFA）评分对 CAP 患者的疾病严重程度进行分层。采用线性回归模型将 SOFA 及 SOFA 特定参数与定量蛋白质组学和代谢组学数据进行关联，模型调整了年龄、BMI、性别、吸烟和技术变量。蛋白质组学和代谢组学分析显示，血浆和血清成分与 CAP 严重程度显著相关。与 SOFA 相关的蛋白质和代谢物与免疫反应有关，特别是与脂质代谢过程有关。与 SOFA 评分相关的蛋白质参与急性期反应、凝血、补体激活和炎症。这些代谢物和蛋白质中的许多不仅与 SOFA 相关，而且与 SOFA 评分的参数相关，这可能反映了肺、肝、肾和心脏功能障碍对代谢组学和蛋白质组学模式的强烈影响。意义：社区获得性肺炎是最常见的感染性疾病，发病率和死亡率高。到目前为止，只有少数研究集中在鉴定与 CAP 严重程度相关的蛋白质或代谢物，且通常基于较小的样本集。筛选新的诊断标志物需要广泛的样本收集，并结合高质量的临床数据。为了鉴定与 CAP 严重程度相关的蛋白质组学和代谢组学模式，我们对一项以 CAP 患者为研究对象的多中心临床研究中的血清和血浆样本进行了代谢组学和蛋白质组学联合检测，这些患者需要住院治疗。该关联研究结果表明，不仅可以通过 SOFA 评分解释分子模式与 CAP 严重程度的变化，还可以将改变的分子分配到呼吸、肾脏、凝血、心血管系统以及肝脏功能障碍。
