Identification of Plasma Proteome Signatures Associated With Surgery Using SOMAscan.

ABSTRACT

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 ≤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). 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.