Identification and validation of a salivary protein panel to detect heart failure early
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ABSTRACT: Background: Over 26 million people suffer from heart failure (HF) globally. Current diagnosis of HF relies on clinical evaluation, blood assays and imaging techniques at the time of diagnosis. Our aim is to develop a diagnostic assay to detect HF early in at risk individuals within the community using human saliva as a medium, paving the way towards precision medicine. Methods: Saliva samples were collected from healthy controls (n=36) and HF patients (n=75). Salivary proteome profiles were analysed by Sequential Window Acquisition of All Theoretical fragment ion spectra – Mass Spectrometry (SWATH-MS). A total of 738 proteins were quantified and 177 proteins demonstrated significant differences in saliva from HF patients and healthy controls. Candidate biomarkers were chosen based on their abundance and difference between the two cohorts. A multi-protein panel was developed using logistic regression analysis. The diagnostic performance of the multi-protein panel was assessed using the receiver operative characteristic curves. The candidate proteins were further validated technically, using western blot analysis as well as biologically, using an independent cohor.t. Results: A group of six proteins were chosen as potential protein candidates based on their differences in the abundance between the two cohorts. During the validation phase, two of the proteins were eliminated as these did not meet our criteria. The panel consists of four proteins with sensitivity of 83.3%, specificity of 62.5% with an area under ROC curve of 0.78 in discriminating healthy controls from NYHA class I/II HF patients. Conclusion: Analysis of salivary proteome using SWATH-MS analysis revealed novel HF-specific protein candidates when combined into a panel yielding high diagnostic performance. A multi-centre longitudinal clinical trial will be the next step before clinical implementation of this panel.
INSTRUMENT(S): TripleTOF 5600
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Saliva
DISEASE(S): Cardiovascular System Disease
SUBMITTER: Xi Zhang
LAB HEAD: Chamindie Punyadeera
PROVIDER: PXD007134 | Pride | 2018-10-24
REPOSITORIES: Pride
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