Circulating long noncoding RNA PDE4DIPP6: A novel biomarker for improving the clinical management of acute coronary syndrome

Abstract

AimLong noncoding RNAs (lncRNAs) have emerged as promising diagnostic biomarkers owing to their dynamic regulation in response to pathological conditions and their detection in clinically relevant samples. Here, we explored the utility of the cardiac expressed and plasma detectable lncRNA PDE4DIPP6 as a biomarker for acute coronary syndrome (ACS). The final goal was to improve the diagnostic efficacy of state-of-the-art tests, particularly the high-sensitivity cardiac troponin assay (hs-cTnT).MethodsThe study enrolled individuals presenting with suspected ACS at the emergency department (ED). LncRNA quantification was performed in plasma samples using RT-qPCR. Discriminatory performance was evaluated by calculating the Area Under the Curve (AUC). Reclassification metrics, including the Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI) indexes, were employed to assess enhancements in diagnostic accuracy.ResultsThe sample comprised 252 patients, 50.8% were diagnosed with ACS and 13.9% with Non-ST Segment Elevation Myocardial Infarction (NSTEMI). Elevated levels of PDE4DIPP6 were observed in ACS patients compared to non-ACS subjects. There was no significant correlation between lncRNA and hs-cTnT levels (rho=0.071), and no association between PDE4DIPP6 levels and potential confounding factors was observed. The inclusion of PDE4DIPP6 on top of troponin T significantly enhanced the discrimination and classification of ACS patients reflected in an improved AUC of 0.734, an IDI of 0.066 and NRI of 0.471. Similarly, elevated levels of the lncRNA were observed in NSTEMI patients compared to ACS patients without NSTEMI. Consistent with previous findings, the addition of PDE4DIPP6 to hs-cTnT improved the discrimination and classification of patients, evident in an increased AUC from 0.859 to 0.944, IDI of 0.237, and NRI of 0.658.ConclusionPDE4DIPP6 offers additional diagnostic insights beyond hs-cTnT, suggesting its potential to improve the clinical management of patients with ACS.