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.