MicroRNAs As Predictors of Chronic Thromboembolic Pulmonary Hypertension

Background: Early recognition towards chronic thromboembolic pulmonary hypertension (CTEPH) after a pulmonary embolism (PE) is very complex due to the insidious nature of the disease and the lack of effective biomarkers. Experts support the application of basic research to develop more agile and faster diagnostic algorithms. Methods: Twenty-two patients with CTEPH, 13 with PE and no diagnosis of either CTEPH or cancer at 2 years-follow-up, and 19 controls were prospectively recruited. Total plasma RNA was isolated and the expression of 179 microRNAs (miRNAs) was quantified. Expression levels were normalized using the most stable miRNA selected by BestRef. Next, we validated the differential panel of miRNAs in an independent cohort of 48 CTEPH, 37 PE and 30 controls. Statistical analysis was performed using R (v3.5.0). Results: A panel of 8 plasma miRNAs was differentially expressed in CTEPH and PE: miR-574-3p, miR-146b-5p, miR-193a-5p, miR-885-5p, miR-122-5p, miR-365a-3p, miR-142-3p and miR-192-5p that we have named as chronic pulmonary thromboepigen (CPT). We obtained a predictive model of CTEPH with the CPT miRNA panel as predictor (AUC = 0,843 (95% CI: 0.758-0.927). Conclusions: The CPT panel could be integrated into the CTEPH algorithm for qualitatively improve diagnosis. More data from large independent and international cohorts about its diagnostic ability are needed for its full generalization. CPT panel was registered in the Spanish Patent and Trademark Office (OEPM)[P202231096]. Funding: ISCIII (PI15/01085)