蛋白质组学标志物与营养风险及营养支持反应的相关性：一项采用非靶向蛋白质组学方法的 EFFORT 试验的二次先导研究。
Association of proteomic markers with nutritional risk and response to nutritional support: A secondary pilot study of the EFFORT trial using an untargeted proteomics approach.
机构信息
Medical University Clinic, Division of Endocrinology, Diabetes & Metabolism, Kantonsspital Aarau, Aarau, Switzerland.
Functional Genomics Center Zurich, ETH and University of Zurich, Zurich, Switzerland.
出版信息
Clin Nutr ESPEN. 2022 Apr;48:282-290. doi: 10.1016/j.clnesp.2022.01.035. Epub 2022 Feb 2.
BACKGROUND
By means of a structured nutritional support intervention, EFFORT showed a risk reduction for adverse events in medical in-patients. We were interested in the prognostic and therapeutic potential of an untargeted proteomics approach to understand response to nutritional support, risk of 30-day mortality, and distinct patterns in severity of malnutrition risk as assessed by the Nutritional Risk screening (NRS 2002), respectively.
METHODS
From 2,088 patients, we randomly took 120 blood samples drawn before treatment initiation on day 1 after hospital admission. Cases were selected by treatment allocation (nutritional support vs. usual nutrition), NRS 2002, and mortality at 30 days, but not on disease type. We measured proteins by untargeted liquid chromatography mass spectrometry (LC-MS/MS).
RESULTS
We found 242 distinct proteins in 120 patients of which 81 (67.5%) survived until day 30. Between group analysis revealed a slight difference between the treatment groups in patients with a NRS 3, but not in those with a higher NRS. C-statistic between non-survivors and survivors at day 30 ranged from 0.60 (95% confidence interval 0.34-0.78) for a combination of 3 proteins/predictors to 0.65 (95% CI 0.53-0.78) for a combination of 32 proteins/predictors. In nutritional support non-survivors, pathway analysis found significant enrichment in pathways for signal transduction, platelet function, immune system regulation, extracellular matrix organization, and integrin cell surface interactions compared to survivors.
CONCLUSION
Within this pilot study using an untargeted proteomics approach, there was only little prognostic and therapeutic potential of proteomics for phenotyping the risk of malnutrition and response to nutritional therapy. The small sample size and high heterogeneity of our population regarding comorbidity burden calls for more targeted approaches in more homogenous populations to understand the true potential of proteomics for individualizing nutritional care.
TRIAL REGISTRATION
This is a pre-planned secondary analysis of the EFFORT trial (ClinicalTrials.gov NCT02517476).
背景
通过结构化的营养支持干预措施，EFFORT 研究显示，它可以降低住院患者不良事件的风险。我们对非靶向蛋白质组学方法的预后和治疗潜力很感兴趣，分别是了解营养支持的反应、30 天死亡率的风险、以及根据营养风险筛查（NRS 2002）评估的营养不良风险严重程度的不同模式。
方法
我们从 2088 名患者中随机抽取 120 名患者，在入院后第 1 天治疗开始前抽取血样。病例是通过治疗分配（营养支持与常规营养）、NRS 2002 和 30 天死亡率选择的，但不是根据疾病类型选择的。我们通过非靶向液相色谱-质谱联用（LC-MS/MS）测量蛋白质。
结果
在 120 名患者中，我们发现了 242 种不同的蛋白质，其中 81 名（67.5%）患者存活至第 30 天。组间分析显示，在 NRS 为 3 的患者中，治疗组之间存在细微差异，但在 NRS 更高的患者中则没有差异。非幸存者和幸存者在第 30 天的 C 统计量范围从 3 种蛋白质/预测因子组合的 0.60（95%置信区间 0.34-0.78）到 32 种蛋白质/预测因子组合的 0.65（95%置信区间 0.53-0.78）。在营养支持的非幸存者中，与幸存者相比，信号转导、血小板功能、免疫系统调节、细胞外基质组织和整合素细胞表面相互作用途径的分析发现显著富集。
结论
在这项使用非靶向蛋白质组学方法的初步研究中，蛋白质组学在表型营养不良风险和对营养治疗的反应方面只有很小的预后和治疗潜力。我们人群的样本量小且合并症负担的异质性高，因此需要在更同质的人群中采用更有针对性的方法，以了解蛋白质组学在个体化营养护理方面的真正潜力。
试验注册
这是 EFFORT 试验（ClinicalTrials.gov NCT02517476）的预先计划的二次分析。
Zotero 插件