Development of a Dynamic Multi-Protein Signature of Postoperative Delirium

Sarinnapha M. Vasunilashorn, Long H. Ngo, Noel Y. Chan, Wenxiao Zhou, Simon T. Dillon, Hasan H. Otu, Sharon K. Inouye, Iris Wyrobnik, George A. Kuchel, Janet E. McElhaney, Zhongcong Xie, David C. Alsop, Richard N. Jones, Towia A. Libermann, Edward R. Marcantonio

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Delirium is common, morbid, and costly, yet its biology is poorly understood. We aimed to develop a multi-protein signature of delirium by identifying proteins associated with delirium from unbiased proteomics and combining them with delirium biomarkers identified in our prior work (interleukin [IL]-6 and IL-2). Methods: We used the Successful Aging after Elective Surgery (SAGES) Study of adults age =70 undergoing major noncardiac surgery (N = 560; 24% delirium). Plasma was collected preoperatively (PREOP) and on postoperative day 2 (POD2). In a nested matched case-control study involving 12 pairs of delirium cases and no-delirium controls, isobaric tags for relative and absolute quantitation-based (iTRAQ) mass spectrometry proteomics was applied to identify the top set of delirium-related proteins. With these proteins, we then conducted enzymelinked immunosorbent assay (ELISA) confirmation, and if confirmed, ELISA validation in 75 matched pairs. Multi-marker conditional logistic regression was used to select the best PREOP and POD2 models for delirium. Results: We identified three proteins from iTRAQ: C-reactive protein (CRP), zinc alpha-2 glycoprotein (AZGP1), and alpha-1 antichymotrypsin (SERPINA3). The best multi-protein models of delirium included: PREOP: CRP and AZGP1 (Bayesian information criteria [BIC]: 93.82, c-statistic: 0.77); and POD2: IL-6, IL-2, and CRP (BIC: 87.11, c-statistic: 0.84). Conclusion: The signature of postoperative delirium is dynamic, with some proteins important before surgery (risk markers) and others at the time of delirium (disease markers). Our dynamic, multi-protein signature for delirium improves our understanding of delirium pathophysiology and may identify patients at-risk of this devastating disorder that threatens independence of older adults.

Original languageEnglish (US)
Pages (from-to)261-268
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume74
Issue number2
DOIs
StatePublished - Jan 16 2019

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Delirium
Proteins
C-Reactive Protein
Immunosorbents
Proteomics
Interleukin-2
Case-Control Studies
Interleukin-6
alpha 1-Antichymotrypsin
Mass Spectrometry

Keywords

  • Delirium
  • Protein signature
  • Proteomics

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Development of a Dynamic Multi-Protein Signature of Postoperative Delirium. / Vasunilashorn, Sarinnapha M.; Ngo, Long H.; Chan, Noel Y.; Zhou, Wenxiao; Dillon, Simon T.; Otu, Hasan H.; Inouye, Sharon K.; Wyrobnik, Iris; Kuchel, George A.; McElhaney, Janet E.; Xie, Zhongcong; Alsop, David C.; Jones, Richard N.; Libermann, Towia A.; Marcantonio, Edward R.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 74, No. 2, 16.01.2019, p. 261-268.

Research output: Contribution to journalArticle

Vasunilashorn, SM, Ngo, LH, Chan, NY, Zhou, W, Dillon, ST, Otu, HH, Inouye, SK, Wyrobnik, I, Kuchel, GA, McElhaney, JE, Xie, Z, Alsop, DC, Jones, RN, Libermann, TA & Marcantonio, ER 2019, 'Development of a Dynamic Multi-Protein Signature of Postoperative Delirium', Journals of Gerontology - Series A Biological Sciences and Medical Sciences, vol. 74, no. 2, pp. 261-268. https://doi.org/10.1093/gerona/gly036
Vasunilashorn, Sarinnapha M. ; Ngo, Long H. ; Chan, Noel Y. ; Zhou, Wenxiao ; Dillon, Simon T. ; Otu, Hasan H. ; Inouye, Sharon K. ; Wyrobnik, Iris ; Kuchel, George A. ; McElhaney, Janet E. ; Xie, Zhongcong ; Alsop, David C. ; Jones, Richard N. ; Libermann, Towia A. ; Marcantonio, Edward R. / Development of a Dynamic Multi-Protein Signature of Postoperative Delirium. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2019 ; Vol. 74, No. 2. pp. 261-268.
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abstract = "Delirium is common, morbid, and costly, yet its biology is poorly understood. We aimed to develop a multi-protein signature of delirium by identifying proteins associated with delirium from unbiased proteomics and combining them with delirium biomarkers identified in our prior work (interleukin [IL]-6 and IL-2). Methods: We used the Successful Aging after Elective Surgery (SAGES) Study of adults age =70 undergoing major noncardiac surgery (N = 560; 24{\%} delirium). Plasma was collected preoperatively (PREOP) and on postoperative day 2 (POD2). In a nested matched case-control study involving 12 pairs of delirium cases and no-delirium controls, isobaric tags for relative and absolute quantitation-based (iTRAQ) mass spectrometry proteomics was applied to identify the top set of delirium-related proteins. With these proteins, we then conducted enzymelinked immunosorbent assay (ELISA) confirmation, and if confirmed, ELISA validation in 75 matched pairs. Multi-marker conditional logistic regression was used to select the best PREOP and POD2 models for delirium. Results: We identified three proteins from iTRAQ: C-reactive protein (CRP), zinc alpha-2 glycoprotein (AZGP1), and alpha-1 antichymotrypsin (SERPINA3). The best multi-protein models of delirium included: PREOP: CRP and AZGP1 (Bayesian information criteria [BIC]: 93.82, c-statistic: 0.77); and POD2: IL-6, IL-2, and CRP (BIC: 87.11, c-statistic: 0.84). Conclusion: The signature of postoperative delirium is dynamic, with some proteins important before surgery (risk markers) and others at the time of delirium (disease markers). Our dynamic, multi-protein signature for delirium improves our understanding of delirium pathophysiology and may identify patients at-risk of this devastating disorder that threatens independence of older adults.",
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AU - Ngo, Long H.

AU - Chan, Noel Y.

AU - Zhou, Wenxiao

AU - Dillon, Simon T.

AU - Otu, Hasan H.

AU - Inouye, Sharon K.

AU - Wyrobnik, Iris

AU - Kuchel, George A.

AU - McElhaney, Janet E.

AU - Xie, Zhongcong

AU - Alsop, David C.

AU - Jones, Richard N.

AU - Libermann, Towia A.

AU - Marcantonio, Edward R.

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N2 - Delirium is common, morbid, and costly, yet its biology is poorly understood. We aimed to develop a multi-protein signature of delirium by identifying proteins associated with delirium from unbiased proteomics and combining them with delirium biomarkers identified in our prior work (interleukin [IL]-6 and IL-2). Methods: We used the Successful Aging after Elective Surgery (SAGES) Study of adults age =70 undergoing major noncardiac surgery (N = 560; 24% delirium). Plasma was collected preoperatively (PREOP) and on postoperative day 2 (POD2). In a nested matched case-control study involving 12 pairs of delirium cases and no-delirium controls, isobaric tags for relative and absolute quantitation-based (iTRAQ) mass spectrometry proteomics was applied to identify the top set of delirium-related proteins. With these proteins, we then conducted enzymelinked immunosorbent assay (ELISA) confirmation, and if confirmed, ELISA validation in 75 matched pairs. Multi-marker conditional logistic regression was used to select the best PREOP and POD2 models for delirium. Results: We identified three proteins from iTRAQ: C-reactive protein (CRP), zinc alpha-2 glycoprotein (AZGP1), and alpha-1 antichymotrypsin (SERPINA3). The best multi-protein models of delirium included: PREOP: CRP and AZGP1 (Bayesian information criteria [BIC]: 93.82, c-statistic: 0.77); and POD2: IL-6, IL-2, and CRP (BIC: 87.11, c-statistic: 0.84). Conclusion: The signature of postoperative delirium is dynamic, with some proteins important before surgery (risk markers) and others at the time of delirium (disease markers). Our dynamic, multi-protein signature for delirium improves our understanding of delirium pathophysiology and may identify patients at-risk of this devastating disorder that threatens independence of older adults.

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