Data-Independent Acquisition Proteomics Identifies Plasma Prostaglandin-H2 D-Isomerase as an Early Diagnostic Biomarker for STEMI and NSTEMI

数据非依赖性采集蛋白质组学鉴定血浆前列腺素H2 D-异构酶为STEMI和NSTEMI的早期诊断生物标志物

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Abstract

Myocardial infarction (MI), including ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI), remains a leading cause of death worldwide. This study aimed to identify the early diagnostic biomarkers for STEMI and NSTEMI. Plasma samples from 386 patients were classified into four groups: control (CON) (n = 62), unstable angina (UA) (n = 62), STEMI (n = 182), and NSTEMI (n = 80). The protein profiles were analyzed using data-independent acquisition (DIA)-based proteomics to identify differentially abundant proteins (DAPs) followed by bioinformatics analysis and ELISA validation. In STEMI, 93 DAPs were detected. Among the selected DAPs that were further validated in a new cohort of patients, prostaglandin-H2 D-isomerase (PTGDS) was elevated at the earliest onset time of STEMI (T1, 1.45 h (95% CI: 1.16-1.73)) or NSTEMI (T1, 1.48 h (95% CI: 0.97-1.98)) while the current biomarkers (hs-TnI, Myo, CK-MB, and BNP) remained within normal ranges. The analysis of diagnostic indices for plasma PTGDS demonstrated a sensitivity of 63.95% and specificity of 65.38% in STEMI, 70% and 71.15% in NSTEMI. Moreover, AUC was 0.61 (95% CI: 0.53-0.69) in STEMI and 0.78 (95% CI: 0.70-0.86) in NSTEMI. The present study demonstrates that in patients with MI, plasma PTGDS increases at an earlier stage of onset time than the current biomarkers, with similar sensitivity and specificity. Therefore, PTGDS has high potential to be developed as an early diagnostic biomarker. In particular, PTGDS might be of greater clinical significance for patients suspected of NSTEMI, for which the biomarker could be more effective in identifying high-risk patients suffering from MI at an early stage.

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