Circulating Long Non-coding RNA ENST00000507296 Is a Prognostic Indicator in Patients with Dilated Cardiomyopathy

Abstract

Background: Long non-coding RNAs (lncRNAs) participate in the pathogenesis of cardiovascular diseases. However, whether circulating lncRNAs serve as dilated cardiomyopathy (DCM) biomarkers remains unclear. Methods: Totally, 266 controls and 818 patients were enrolled. First, microarray-based circulating lncRNA profiling was performed in 10 normal controls and 10 patients with DCM. Second, the top 20 differentially expressed lncRNAs were validated by real-time qPCR in 64 controls and 64 DCM patients. Moreover, lncRNA sequencing was performed in three human heart-derived cell types, and the correlation between circulating lncRNA levels and the severity of heart failure was evaluated in the validated population. The validated two lncRNAs were assessed in 198 DCM patients and 198 matched controls. Finally, the sensitivity and specificity of circulating lncRNA expression in DCM diagnosis were evaluated using receiver-operating characteristic curve analysis, while Cox regression and Kaplan-Meier curve analysis were further performed in 552 DCM patients. Results: Eight candidate lncRNA biomarkers were obtained after microarray screening and real-time PCR validation. Among them, five were validated in the second cohort. However, only the levels of circulating lncRNA ENST00000507296 and ENST00000532365 were significantly correlated with the cardiac function, as well as detectable in at least one of the human heart-derived cell types by lncRNA-seq. Importantly, low circulating ENST00000507296 level was associated with high event-free survival in patients with DCM. Conclusions: Circulating lncRNA ENST00000507296 was a prognostic biomarker in patients with DCM.

Identification of differentially expressed long non-coding RNAs associated with dilated cardiomyopathy using integrated bioinformatics approaches

“…DCM accounts for about one-third of heart failure patients. A recent study reported that lncRNAs ENST00000532365 and ENST00000507296 could serve as biomarkers for the diagnosis of DCM-related heart failure (36). In the present study, we found that XIST presented an AUC of 0.733, and IDI2-AS1 exhibited an AUC of 0.796.…”

“…DCM is usually diagnosed at ages between 30 and 40 years of age. However, owing to the vague symptoms and delay in diagnosis, the outcome for DCM is poor (36). DCM accounts for about one-third of heart failure patients.…”

Genomic analysis of circular RNAs in heart

“…Arrows point to the transcriptional directions of MYH6 and MYH7 genes. (D) Heatmap illustrates the rank of the average expression across all studied samples for circRNAs produced from MYH6 and MYH7 genes in this study, and in human, mouse and rat hearts as identi ed by Tan et al [12] and Werfel et al [11]. The…”

“…Analysis of circRNAs from MYH6 and MYH7 gene. (A) Schematic diagram showing a number of rt-circRNAs originate from MYH6 and MYH7 genes in human heart identi ed in this study, study of Tan et al [12] and Werfel et al [11], and in (B) mouse heart identi ed in this study and study of Werfel et al [11], as well as in (C) rat heart revealed in the study of Werfel et al [11]. Arrows point to the transcriptional directions of MYH6 and MYH7 genes.…”

Genomic analysis of circular RNAs in heart

“…Therefore, it is likely that other unknown genetic factors await discovery. The aberrant expression of different types of RNA transcripts, including those transcribed from protein coding genes [ 7 – 9 ], long non-coding genes [ 10 , 11 ] and miRNAs [ 12 – 14 ], have been observed in DCM.…”