Identification of Plasma Proteome Signatures Associated With Surgery Using SOMAscan
Identification of Plasma Proteome Signatures Associated With Surgery Using SOMAscan
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DOI：
10.1097/sla.0000000000003283
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发表时间：
2021-04-01
影响因子：
9
通讯作者：
Libermann, Towia A.
中科院分区：
文献类型：
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作者：
Fong, Tamara G.;Chan, Noel Y.;Libermann, Towia A.
目的：描述老年人手术的蛋白质组特征及其与术后结局的关系。背景资料概述：循环血浆蛋白可以反映手术后的生理反应和临床结局。方法：使用SOMAscan分析接受择期手术的老年人血浆中的1305种蛋白质。手术相关蛋白进行了免疫途径分析。使用Luminex或酶联免疫吸附测定方法对选定的手术相关蛋白进行独立验证。广义线性模型估计与术后结果的相关性。结果：来自择期手术后成功老化（SAGES）研究的子队列（n = 36）的血浆用于SOMAscan。术后第2天（POD 2）和术前（PREOP）之间Benjamini-Hochberg（BH）校正P值= 1.5的110种蛋白质的系统生物学分析确定了对促炎蛋白质有主要影响的功能途径。几丁质酶-3样蛋白1（CHI 3L 1）、C反应蛋白（CRP）和白细胞介素-6（IL-6）在SAGES的单独验证队列中进行了独立验证（CRP、IL-6 n = 150; CHI 3L 1 n = 126）。CHI 3L 1和IL-6的倍数变化与术后并发症增加相关[相对风险（RR）1.50，95%置信区间（95% CI）1.21-1.85和RR 1.63，95% CI 1.18-2.26]，住院时间（RR 1.35，95% CI 0.77-1.92和RR 0.98，95% CI 0.52-1.45）和出院至急性后设施的风险（RR 1.15，95% CI 1.04-1.26和RR 1.11，95% CI 1.04-1.18）; POD 2和PREOP CRP差异与出院至急性后设施相关（RR 1.14，95% CI 1.04-1.25）。结论：SOMAscan可以识别新的和临床相关的手术诱导的蛋白质变化。最终，蛋白质组学可以提供有关手术应激对术后结果的影响途径的见解。
Objectives: To characterize the proteomic signature of surgery in older adults and association with postoperative outcomes. Summary of Background Data: Circulating plasma proteins can reflect the physiological response to and clinical outcomes after surgery. Methods: Blood plasma from older adults undergoing elective surgery was analyzed for 1305 proteins using SOMAscan. Surgery-associated proteins underwent Ingenuity Pathways Analysis. Selected surgery-associated proteins were independently validated using Luminex or enzyme-linked immunosorbent assay methods. Generalized linear models estimated correlations with postoperative outcomes. Results: Plasma from a subcohort (n = 36) of the Successful Aging after Elective Surgery (SAGES) study was used for SOMAscan. Systems biology analysis of 110 proteins with Benjamini-Hochberg (BH) corrected P value = 1.5 between postoperative day 2 (POD2) and preoperative (PREOP) identified functional pathways with major effects on pro-inflammatory proteins. Chitinase-3-like protein 1 (CHI3L1), C-reactive protein (CRP), and interleukin-6 (IL-6) were independently validated in separate validation cohorts from SAGES (n = 150 for CRP, IL-6; n = 126 for CHI3L1). Foldchange CHI3L1 and IL-6 were associated with increased postoperative complications [relative risk (RR) 1.50, 95% confidence interval (95% CI) 1.21-1.85 and RR 1.63, 95% CI 1.18-2.26, respectively], length of stay (RR 1.35, 95% CI 0.77-1.92 and RR 0.98, 95% CI 0.52-1.45), and risk of discharge to postacute facility (RR 1.15, 95% CI 1.04-1.26 and RR 1.11, 95% CI 1.04-1.18); POD2 and PREOP CRP difference was associated with discharge to postacute facility (RR 1.14, 95% CI 1.04-1.25). Conclusion: SOMAscan can identify novel and clinically relevant surgery-induced protein changes. Ultimately, proteomics may provide insights about pathways by which surgical stress contributes to postoperative outcomes.