Circulating long noncoding RNA PDE4DIPP6: A novel biomarker for improving the clinical management of non-ST-segment elevation myocardial infarction

• Published in: Clinica chimica acta 2024-07, Vol.561, p.119840, Article 119840
• Main Authors: Koch, Pia F., García-Hidalgo, María C., Labus, Josephine, Biener, Moritz, Thum, Thomas, de Gonzalo-Calvo, David, Bär, Christian
• Format: Article
• Language: English
• Subjects: Acute Coronary Syndrome; Biomarkers; Long noncoding RNA; Noncoding RNA; NSTEMI
• ISSN: 0009-8981; 1873-3492; 1873-3492
• DOI: 10.1016/j.cca.2024.119840

•What is already known:•Hs-cTnT assays exhibit remarkable sensitivity but often compromise specificity.•Augmenting hs-cTnT with supplementary parameters is imperative to refine specificity in AMI management.•What this study adds:•Circulating levels of lncRNA PDE4DIPP6 are independently associated with both ACS and NSTEMI-ACS.•The addition of PDE4DIPP6 to hs-cTnT significantly improves the discrimination and classification accuracy for NSTEMI.•LncRNAs emerge as promising markers to improve the diagnostic precision of existing cardiac tests. Long noncoding RNAs (lncRNAs) have emerged as promising diagnostic biomarkers. Here, we investigated the cardiac-expressed and plasma-detectable lncRNA PDE4DIPP6 as a biomarker for non-ST-segment elevation myocardial infarction (NSTEMI), specifically assessing its potential to enhance the diagnostic efficacy of high-sensitivity cardiac troponin (hs-cTnT). The study enrolled individuals presenting with suspected acute coronary syndrome (ACS). LncRNA quantification was performed in plasma samples using RT-qPCR. The discriminatory performance was assessed by calculating the Area Under the Curve (AUC). Reclassification metrics, including the Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI) indexes, were utilized to evaluate enhancements in diagnostic accuracy. Among the 252 patients with suspected ACS, 50.8 % were diagnosed with ACS, and 13.9 % with NSTEMI. Initially, the association of lncRNA PDE4DIPP6 with ACS was investigated. Elevated levels of this lncRNA were observed in ACS patients compared to non-ACS subjects. No association was found between lncRNA PDE4DIPP6 levels and potential confounding factors, nor was a significant correlation with hs-cTnT levels (rho = 0.071). The inclusion of lncRNA PDE4DIPP6 on top of hs-cTnT significantly improved the discrimination and classification of ACS patients, as reflected by an enhanced AUC of 0.734, an IDI of 0.066 and NRI of 0.471. Subsequently, the lncRNA PDE4DIPP6 was evaluated as biomarker of NSTEMI. Elevated levels of the lncRNA were observed in NSTEMI patients compared to patients without NSTEMI. Consistent with previous findings, the addition of lncRNA PDE4DIPP6 to hs-cTnT improved the discrimination and classification of patients, increasing the AUC from 0.859 to 0.944, with an IDI of 0.237 and NRI of 0.658. LncRNA PDE4DIPP6 offers additional diagnostic insights beyond hs-cTnT, suggesting its potential to improve the clinical managem