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Multiple Non-coding ANRIL Transcripts Are Associated with Risk of Coronary Artery Disease: a Promising Circulating
Juan Fang1, Zhicheng Pan1, Dongfei Wang1
1Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
Insights
This study investigated ANRIL isoforms in coronary artery disease (CAD). Circulating circANRIL(exon14-4) showed potential as a biomarker for diagnosing CAD and predicting major adverse cardiovascular events (MACE).
Area of Science:
- Molecular Biology
- Cardiovascular Disease Research
- Biomarker Discovery
Background:
- ANRIL is a long non-coding RNA with multiple transcriptional isoforms.
- Dysregulation of ANRIL isoforms is implicated in various diseases, including cardiovascular conditions.
- The diagnostic and prognostic utility of specific ANRIL isoforms in coronary artery disease (CAD) requires further investigation.
Purpose of the Study:
- To explore the diagnostic value of six ANRIL transcriptional isoforms in patients with coronary artery disease (CAD).
- To identify the most promising ANRIL isoform as a circulating biomarker for CAD.
- To evaluate the prognostic value of the identified biomarker in relation to clinical outcomes and major adverse cardiovascular events (MACE).
Main Methods:
- Selection and measurement of six target ANRIL isoforms' expression in peripheral blood of CAD patients and controls.
- Evaluation of diagnostic performance of individual ANRIL isoforms.
- Validation of the diagnostic and prognostic value of the best-performing isoform in a larger clinical cohort.
- Correlation analysis between circANRIL(exon14-4) expression levels and MACE incidence.
Main Results:
- lncANRIL(exon1) and lncANRIL(exon4-6) were significantly increased in CAD patients, while circANRIL(exon14-4) was downregulated.
- circANRIL(exon14-4) demonstrated the highest diagnostic value among the evaluated isoforms.
- Lower expression of circANRIL(exon14-4) was significantly associated with an increased incidence of MACE.
- Combination of circANRIL(exon14-4) with other factors improved CAD patient differentiation.
Conclusions:
- circANRIL(exon14-4) exhibits significant diagnostic value for coronary artery disease.
- Downregulation of circANRIL(exon14-4) is linked to increased risk and severity of CAD.
- circANRIL(exon14-4) represents a promising circulating biomarker for both the diagnosis and prognosis of CAD.
Abstract:
Multiple ANRIL transcriptional isoforms, such as lncANRIL and circANRIL have been identified. We sought to explore their diagnostic value in patients with coronary artery disease (CAD). First, we selected six target ANRIL isoforms and measured their expression in CAD patients and controls in the peripheral blood. Their diagnostic values were evaluated. circANRIL(exon14-4) was identified as the best potential biomarker. Afterwards, we validated its diagnostic value and evaluated its prognostic value in a larger clinical cohort. Among six tested ANRILs, lncANRIL(exon1) and lncANRIL(exon4-6) in the CAD patients were significantly increased, while circANRIL(exon14-4) was downregulated. circANRIL(exon14-4) had the highest diagnostic value among the three isoforms. The combination of circANRIL(exon14-4) and other factors resulted in a more accurate differentiation of CAD patients. Moreover, lower expression of circANRIL(exon14-4) was associated with higher incidence of MACE. circANRIL(exon14-4) is closely associated with CAD risk and severity, which provides a promising circulating biomarker for CAD diagnosis and prognosis.
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