High‐throughput serum proteomics for the identification of protein biomarkers of mortality in older men
Year: 2018
Type: article
Abstract: The biological perturbations associated with incident mortality are not well elucidated, and there are limited biomarkers for the prediction of mortality. We used a novel high-throughput proteomics approach to identify serum peptides and proteins associated with 5-year mortality in community-dwelling men age ≥65 years who participated in a longitudinal observational study of musculoskeletal aging (Osteoporotic Fractures in Men: MrOS). In a discovery phase, serum specimens collected at baseline in 2473 men were analyzed using liquid chromatography-ion mobility-mass spectrometry, and incident mortality in the subsequent 5 years was ascertained by tri-annual questionnaire. Rigorous statistical methods were utilized to identify 56 peptides (31 proteins) that were associated with 5-year mortality. In an independent replication phase, selected reaction monitoring was used to examine 21 of those peptides in baseline serum from 750 additional men; 81% of those peptides remained significantly associated with mortality. Mortality-associated proteins included a variety involved in inflammation or complement activation; several have been previously linked to mortality (e.g., C-reactive protein, alpha 1-antichymotrypsin) and others are not previously known to be associated with mortality. Other novel proteins of interest included pregnancy-associated plasma protein, VE-cadherin, leucine-rich α-2 glycoprotein 1, vinculin, vitronectin, mast/stem cell growth factor receptor, and Saa4. A panel of peptides improved the predictive value of a commonly used clinical predictor of mortality. Overall, these results suggest that complex inflammatory pathways, and proteins in other pathways, are linked to 5-year mortality risk. This work may serve to identify novel biomarkers for near-term mortality.
Source: Aging Cell
DOI: 10.1111/acel.12717
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,790
Awards: G1101846420, G187300890, Osteoporotic Fractures in Men, G288989767, G2961663205, G3049017749, Osteoporotic Fractures in Men - MrOS Renewal, Osteoporotic Fractures in Men, G4276072587, Sex Differences in Musculoskeletal Conditions across the Lifespan, G5246217528, G5370920299, G5608475838, A Research Resource for Ultra-sensitive High Throughput Proteomics, G585648573, G659495149, G7771580635, Mineralization Gene Variants: Biochemical Implications and Associations with BMD, G801436702, G8243955340, G9000021615, G9000036658, G9000058914, G9000064213, G9000085452, G9000121640, G9000122217, G9000129730, G9000291326
OpenAlex ID: W2789620702