Dataset Information

Dysregulated Circulating Apoptosis- and Autophagy-Related lncRNAs as Diagnostic Markers in Coronary Artery Disease.

ABSTRACT:

Objective

Increasing evidence emphasizes the implications of dysregulated apoptosis and autophagy cellular processes in coronary artery disease (CAD). Herein, we aimed to explore apoptosis- and autophagy-related long noncoding RNAs (lncRNAs) in peripheral blood of CAD patients.

Methods

The mRNA and lncRNA expression profiles were retrieved from the Gene Expression Omnibus (GEO) database. With ∣fold change | >1.5 and adjusted p value < 0.05, differentially expressed apoptosis- and autophagy-related mRNAs were screened between CAD and healthy blood samples. Also, differentially expressed lncRNAs were identified for CAD. Using the psych package, apoptosis- and autophagy-related lncRNAs were defined with Spearson's correlation analysis. Receiver operating characteristic (ROC) curves were conducted for the assessment of the diagnosed efficacy of these apoptosis- and autophagy-related lncRNAs.

Results

Our results showed that 24 apoptosis- and autophagy-related mRNAs were abnormally expressed in CAD than normal controls. 12 circulating upregulated and 1 downregulated apoptosis- and autophagy-related lncRNAs were identified for CAD. The ROCs confirmed that AC004485.3 (AUC = 0.899), AC004920.3 (AUC = 0.93), AJ006998.2 (AUC = 0.776), H19 (AUC = 0.943), RP5-902P8.10 (AUC = 0.956), RP5-1114G22.2 (AUC = 0.883), RP11-247A12.1 (AUC = 0.885), RP11-288L9.4 (AUC = 0.928), RP11-344B5.2 (AUC = 0.858), RP11-452C8.1 (AUC = 0.929), RP11-565A3.1 (AUC = 0.893), and XXbac-B33L19.4 (AUC = 0.932) exhibited good performance in differentiating CAD from healthy controls.

Conclusion

Collectively, our findings proposed that circulating apoptosis- and autophagy-related lncRNAs could become underlying diagnostic markers for CAD in clinical practice.

SUBMITTER: Zhang L

PROVIDER: S-EPMC8426068 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Circular RNA (circRNA) has been reported to be involved in the pathogenesis of cardiovascular disease (CVD), however, it is unclear whether circRNA carried by exosomes (exos) can be used as biomarkers for chronic coronary syndrome (CCS). This study aimed to investigate the expression pattern of exosomal circRNAs in the plasma of CCS patients, and to screen exo-circRNAs that can act as biomarkers for the diagnosis of CCS. Methods: High-throughput sequencing technology was carried out in the plasma exosomal RNA of 15 CCS patients and 15 non-cardiac chest pain patients (NCCP, control group) (sequencing cohort) to screen for differentially expressed circRNAs. Selected differentially expressed exo-circRNAs were further verified by real time polymerase chain reaction (RT-PCR) in a small-sample cohort (derivation cohort) and a large-sample cohort (validation cohort). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of exo-circRNAs for CCS patients. Results: By high-throughput sequencing of circRNAs in 15 CCS patients and 15 NCCP patients, 276 circRNAs differentially expressed in plasma exosomes of CCS patients were screened by using |log2(Fold change) |>1 and q-value<0.001, and 103 were up-regulated and 173 were down-regulated. Among the 103 up-regulated circRNAs, 5 circRNAs with high expression levels and significantly increased in plasma exosomes of CCS patients were selected for validation. Twice RT-PCR validation demonstrated that exo-hsa_circ_0075269 and exo-hsa_circ_0000284 were significantly up-regulated in patients with CCS (P<0.001). Circulating exo-hsa_circ_0075269 and exo-hsa_circ_0000284 yielded the area under the curve (AUC) values of 0.761 (P<0.001, 95%CI=0.669, 0.852) and 0.623 (P=0.015, 95%CI=0.522, 0.724) for CCS, respectively by ROC curve analysis. Moreover, AUC of hsa_circ_0075269 combined with hsa_circ_0000284 for diagnosing CCS was 0.741 (P<0.001, 95%CI=0.667, 0.850). Conclusion: The expression profile of circRNA in plasma exosomes of patients with CCS was significantly different from that of the control group. Plasma exo-hsa_circ_0075269 and exo-hsa_circ_0000284 have the potential to be new biomarkers for CCS diagnosis.