Discovery of novel plasma protein biomarkers to predict imminent cystic fibrosis pulmonary exacerbations using multiple reaction monitoring mass spectrometry

Thorax
Bradley S QuonDon D Sin

Abstract

Despite the significant morbidity and mortality related to pulmonary exacerbations in cystic fibrosis (CF), there remains no reliable predictor of imminent exacerbation. To identify blood-based biomarkers to predict imminent (<4 months from stable blood draw) CF pulmonary exacerbations using targeted proteomics. 104 subjects provided plasma samples when clinically stable and were randomly split into discovery (n=70) and replication (n=34) cohorts. Multiple reaction monitoring mass spectrometry (MRM-MS) was used to measure 117 peptides (79 proteins) from plasma. Plasma proteins with differential abundance between subjects who did versus did not develop an imminent exacerbation were analysed and proteins with fold difference >1.5 between the groups were included in an MRM-MS classifier model to predict imminent exacerbations. Performance characteristics were compared with clinical predictors and candidate plasma protein biomarkers. Six proteins were included in the final MRM-MS protein panel. The area under the curve (AUC) for the prediction of imminent exacerbations was highest for the MRM-MS protein panel (AUC 0.74) in comparison to FEV1% predicted (AUC 0.55) and the top candidate plasma protein biomarkers, including C-reactive...Continue Reading

References

Feb 24, 2001·American Journal of Epidemiology·T G LiouB C Marshall
Oct 31, 2002·American Journal of Respiratory and Critical Care Medicine·Nicole Mayer-HamblettMoira L Aitken
May 2, 2006·Statistical Applications in Genetics and Molecular Biology·Gordon K Smyth
Jan 9, 2007·Respirology : Official Journal of the Asian Pacific Society of Respirology·David W ReidE Haydn Walters
Jul 22, 2008·The Journal of Pediatrics·Philip M FarrellUNKNOWN Cystic Fibrosis Foundation
May 5, 2009·Molecular & Cellular Proteomics : MCP·Michael A KuzykChristoph H Borchers
May 14, 2010·American Journal of Respiratory and Critical Care Medicine·Don B SandersChristopher H Goss
Jul 14, 2010·BMC Biology·Damien ChaussabelJacques Banchereau
Jun 17, 2011·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·D BiltonK De Boeck
Dec 21, 2012·Pediatric Pulmonology·Gregory S SawickiLizheng Shi
Dec 28, 2012·Nature Methods·Michael A Gillette, Steven A Carr
Feb 12, 2013·The European Respiratory Journal·Craig E WheelockUNKNOWN U-BIOPRED Study Group
Apr 2, 2013·American Journal of Respiratory and Critical Care Medicine·Peter J MogayzelUNKNOWN Pulmonary Clinical Practice Guidelines Committee
Jun 15, 2013·Methods in Molecular Biology·Michael A KuzykChristoph H Borchers
Jun 26, 2013·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·David LinUNKNOWN Networks of Centres of Excellence, Centres of Excellence for Commercialization and Research-Prevention of Organ Failure Cent
Jul 23, 2013·Chest·Alborz Hakimi ShokiBradley S Quon
Feb 28, 2014·European Journal of Heart Failure·Zsuzsanna HollanderUNKNOWN NCE CECR PROOF Prevention of Organ Failure (PROOF) Centre of Excellence

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Citations

Jun 15, 2016·Annals of the American Thoracic Society·Andrew Bush
Mar 17, 2017·Expert Review of Respiratory Medicine·Robert D GrayClifford C Taggart
Apr 30, 2017·Proteomics. Clinical Applications·Emily M DeBoerRobin R Deterding
Jul 28, 2017·Analytical Chemistry·Xu ZhangDaniel Figeys
May 1, 2018·Environmental Science and Pollution Research International·Hongxiang MuLan Yi
Oct 13, 2018·Annual Review of Medicine·Michael M ReyDenis Hadjiliadis
May 7, 2019·Expert Review of Molecular Diagnostics·Georgia KontostathiAntonia Vlahou
Jun 17, 2020·Expert Review of Respiratory Medicine·Claire J HoustonDamian G Downey
Oct 6, 2020·Frontiers in Pharmacology·Lucy Perrem, Felix Ratjen
Aug 6, 2020·International Journal of Molecular Sciences·Nara LiessiClarissa Braccia
Jun 2, 2020·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·David JungBradley S Quon
Dec 25, 2019·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Scott D SagelMarianne S Muhlebach
Mar 25, 2019·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Laura J SherrardMichael M Tunney
Oct 24, 2018·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Clarissa BracciaAndrea Armirotti
Feb 22, 2017·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Marianne S MuhlebachScott D Sagel

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