2015CAOHUYTPhD.pdf (5.03 MB)
The plasma proteome and outcome in patients with heart failure
thesisposted on 2015-06-30, 11:10 authored by Cao Huy Thong
Heart failure is a complex clinical syndrome that occurs at the end stage of heart disease with high costs and poor outcomes. Despite advances in therapy, improving clinical outcomes remains a challenge for physicians with 50% of patients dying within 5 years. The main aim of this study was to discover novel biomarkers in plasma that could predict treatment response in patients with heart failure using plasma proteomics. The use of two dimensional liquid chromatography coupled to electrospray ionisation tandem mass spectrometry in high definition ion mobility combined with a multiple affinity removal system column and immunoluminometric assay discovered CD180 antigen, Heat shock 70 kDa protein 4L, Leukemia inhibitory factor receptor and Neurotrimin as novel biomarkers which are able to predict treatment response in patients with heart failure. Moreover, Thyroid receptor interacting protein 11, Patatin like phospholipase domain containing protein 2 and Mannan binding lectin serine protease 2 were identified as novel biomarkers for prediction of death in patients with heart failure. Furthermore, two multiple biomarker models were developed from the findings obtained of using matrix assisted laser desorption ionisation mass spectrometry combined with C18 solid phase extraction which are able to predict treatment response in patients with heart failure. The model with seven peptide peaks showed an excellent area under the receiver operating characteristic curve (AUC) of 0.907. In particular, the model with seventeen peptide peaks achieved the maximum AUC of 1.000 (100% sensitivity and 100% specificity). The discovery of novel biomarkers in this study not only adds information to understand the pathophysiological mechanisms of heart failure better, but also may provide a more accurate prediction of treatment response to guide medical therapy. This may enable the practice of stratified medicine in the future. Moreover, novel therapeutic targets could be identified for design of new drugs to improve outcomes.
Supervisor(s)Ng, Leong Loke; Jones, Don
Date of award2015-06-01
Author affiliationDepartment of Cardiovascular Sciences
Awarding institutionUniversity of Leicester