Proteomics

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Identification of candidate circulating glucocorticoid response biomarkers in humans using a proteomic approach

ABSTRACT: Context Glucocorticoids used in pharmacological doses for the treatment of a variety of medical conditions, and endogenous glucocorticoid excess – Cushing’s syndrome, may result in several adverse effects, but currently there is no clinically useful biomarker of glucocorticoid activity. Objective To identify glucocorticoid-responsive proteins potentially measurable in human serum. Setting and Design A three-phase protein biomarker discovery strategy was used. Proteomic biomarker discovery and qualification was conducted on the secretome of ex vivo-stimulated peripheral blood mononuclear cells (PBMC) isolated from 6 volunteers, incubated ± dexamethasone 100 ng/mL for 4h and 24h. Untargeted proteomics with label-free quantification (LFQ) was conducted to discover candidate proteins which were quantified using targeted proteomics by a custom multiple reaction monitoring mass spectrometry (MRM-MS) assay. Five proteins were selected for serum measurement by immunoassay in 20 healthy volunteers, with blood drawn at baseline and 12h after 4 mg oral dexamethasone.

ORGANISM(S): Homo Sapiens

SUBMITTER: Ahmed Mohamed  

PROVIDER: PXD019972 | panorama | Mon Mar 15 00:00:00 GMT 2021

REPOSITORIES: PanoramaPublic

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Ex vivo glucocorticoid-induced secreted proteome approach for discovery of glucocorticoid-responsive proteins in human serum.

Inder Warrick J WJ   Mohamed Ahmed A   Keshvari Sahar S   Barclay Johanna L JL   Ruelcke Jayde E JE   Stoll Thomas T   Nolan Brendan J BJ   Cesana-Nigro Nicole N   Hill Michelle M MM  

Proteomics. Clinical applications 20210312 2-3

<h4>Purpose</h4>To identify glucocorticoid-responsive proteins measurable in human serum that may have clinical utility in therapeutic drug monitoring and the diagnosis of cortisol excess or deficiency.<h4>Experimental design</h4>A phased biomarker discovery strategy was conducted in two cohorts. Secretome from peripheral blood mononuclear cells (PBMC) isolated from six volunteers after ex vivo incubation ± dexamethasone (DEX) 100 ng/mL for 4 h and 24 h was used for candidate discovery and quali  ...[more]

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