• Tamara G Fong, Noel Y Chan, Simon T Dillon, Wenxiao Zhou, Bridget Tripp, Long H Ngo, Hasan H Otu, Sharon K Inouye, Sarinnapha M Vasunilashorn, Zara Cooper, Zhongcong Xie, Edward R Marcantonio, and Towia A Libermann.
• Aging Brain Center, Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA.
• Ann. Surg. 2021 Apr 1; 273 (4): 732-742.

ObjectivesTo characterize the proteomic signature of surgery in older adults and association with postoperative outcomes.Summary Of Background DataCirculating plasma proteins can reflect the physiological response to and clinical outcomes after surgery.MethodsBlood 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.ResultsPlasma 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 ≤0.01 and an absolute foldchange (|FC|) ≥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).ConclusionSOMAscan 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.Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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