Circulating circRNA as Biomarkers For Dilated Cardiomyopathy Etiology

Background: Dilated cardiomyopathy (DCM) is the third most common cause of heart failure. The multidisciplinary nature of testing, -involving genetics, imaging, or cardiovascular techniques-, makes its diagnosis challenging. Novel and reliable biomarkers are needed for early identification and tailored personalized management. Peripheral circular RNAs (circRNAs), a leading research topic, remain mostly unexplored in DCM. We aimed to assess whether peripheral circRNAs are expressed differentially among etiology-based DCM. The study was based on a case-control multicentric study. Methods: We enrolled 130 subjects: healthy controls (n=20), idiopathic DCM (n=30), ischemic DCM (n=20) and familial DCM patients which included pathogen variants of i) LMNA gene (n=30) and ii) BCL2-associated athanogene 3 (BAG3) gene (n=30). Differentially expressed circRNAs were analyzed in plasma samples by quantitative RT-PCR and correlated to relevant systolic and diastolic parameters. The pathophysiological implications were explored through bioinformatics tools. Results: Four circRNAs were overexpressed compared to controls: hsa_circ_0003258, hsa_circ_0051238, and hsa_circ_0051239 in LMNA-related DCM; and hsa_circ_0089762 in the ischemic DCM cohort. The obtained areas under the curve confirm the discriminative capacity of circRNAs. Conclusions: The circRNAs correlated with some diastolic and systolic echocardiographic parameters with notable diagnostic potential in DCM. Circulating circRNAs may be helpful for the etiology-based diagnosis of DCM as a non-invasive biomarker.