Identification and Validation of Novel Biomarkers for Unstable Angina Using Olink Proteomics

Unstable angina (UA) represents a prevalent cardiovascular
condition
characterized by significant morbidity and mortality, necessitating
the development of effective early diagnostic biomarkers. This study
sought to identify plasma protein biomarkers associated with UA utilizing
Olink proteomics. A cohort of 120 participants, comprising 60 individuals
diagnosed with UA and 60 healthy controls, was recruited. A total
of 92 inflammation-related plasma proteins were quantified through
a proximity extension assay. In the discovery cohort, differential
expression analysis revealed significant alterations in 49 proteins,
which were predominantly enriched in cytokine-mediated signaling and
MAPK pathways, as demonstrated by Gene Ontology and Kyoto Encyclopedia
of Genes and Genomes analyses. Least absolute shrinkage and selection
operator regression and random forest methodologies prioritized three
biomarkersSPON2, PTX3, and GBGT1that exhibited elevated
levels in UA patients compared to controls. Receiver operating characteristic
analysis demonstrated area under the curve values of 0.859, 0.937,
and 0.900 for SPON2, PTX3, and GBGT1, respectively. A combined diagnostic
model incorporating these three proteins achieved an AUC of 0.979
and demonstrated robust performance in an independent validation cohort.
These results suggest that SPON2, PTX3, GBGT1, and their composite
model hold promise as diagnostic biomarkers for UA.