Koch Pia F, García-Hidalgo María C, Labus Josephine, Biener Moritz, Thum Thomas, de Gonzalo-Calvo David, Bär Christian
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Surgery, Experimental Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Berlin, Germany.
Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain; CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain.
Clin Chim Acta. 2024 Jul 15;561:119840. doi: 10.1016/j.cca.2024.119840. Epub 2024 Jun 29.
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 management of patients with NSTEMI.
长链非编码RNA（lncRNAs）已成为有前景的诊断生物标志物。在此，我们研究了心脏表达且可在血浆中检测到的lncRNA PDE4DIPP6作为非ST段抬高型心肌梗死（NSTEMI）的生物标志物，特别评估其增强高敏心肌肌钙蛋白（hs-cTnT）诊断效能的潜力。
本研究纳入疑似急性冠状动脉综合征（ACS）的患者。使用逆转录定量聚合酶链反应（RT-qPCR）对血浆样本进行lncRNA定量分析。通过计算曲线下面积（AUC）评估鉴别性能。利用包括综合鉴别改善（IDI）和净重新分类改善（NRI）指数在内的重新分类指标来评估诊断准确性的提高。在252例疑似ACS患者中，50.8%被诊断为ACS，13.9%被诊断为NSTEMI。最初，研究了lncRNA PDE4DIPP6与ACS的关联。与非ACS受试者相比，ACS患者中该lncRNA水平升高。未发现lncRNA PDE4DIPP6水平与潜在混杂因素之间存在关联，也未发现与hs-cTnT水平有显著相关性（rho = 0.071）。在hs-cTnT基础上加入lncRNA PDE4DIPP6显著改善了ACS患者的鉴别和分类，AUC提高到0.734，IDI为0.066，NRI为0.471。随后，评估lncRNA PDE4DIPP6作为NSTEMI生物标志物的情况。与无NSTEMI的患者相比，NSTEMI患者中lncRNA水平升高。与先前研究结果一致，在hs-cTnT中加入lncRNA PDE4DIPP6改善了患者的鉴别和分类，AUC从0.859增加到0.944，IDI为0.237，NRI为0.658。
lncRNA PDE4DIPP6提供了超越hs-cTnT的额外诊断信息，表明其有改善NSTEMI患者临床管理的潜力。
