Prognostic value of peripheral blood circular RNAs in patients with acute coronary syndrome

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Abstract

Background

Acute coronary syndrome (ACS) is a clinical emergency. Although its prognosis has been significantly improved, some patients will have major adverse cardiovascular events (MACE) in the short term. We aimed to analyze the prognostic value of circRNAs in patients with ACS.

Methods

This diagnostic accuracy study enrolled a total of 100 patients with ACS from January 2019 to January 2021. All patients were followed up for 30 days. The expression of circRNAs in peripheral blood was determined using real-time fluorescence quantification PCR (qRT-PCR). 30 patients with MACE were divided into the observation group and 70 patients without MACE were divided into the control group. The general data and the detection results of circRNAs of the two groups were compared, and the influencing factors of MACE in ACS patients were analyzed by logistic regression. Receiver operating characteristic (ROC) curves were generated, and the predictive value of peripheral blood circRNAs for MACE in patients with ACS was evaluated.

Results

The age, sex, hypertension, dyslipidemia, location of coronary artery disease, left ventricular ejection fraction, and Killip grade were not significantly different between the two groups (P>0.05). Type 2 diabetes and smoking history in the observation group were also comparable between the two groups (P>0.05). Logistic regression analysis showed that type 2 diabetes mellitus [odd ratio (OR) 1.314, 95% confidence interval (CI): 1.052–1.437, P=0.002], smoking history (OR 1.227, 95% CI: 1.014–1.385, P=0.001), and the up-regulation of circRNAs in peripheral blood (OR 1.312, 95% CI: 1.028–1.452, P=0.002) were risk factors for MACE in ACS patients. The results of the ROC curve showed that peripheral blood circRNAs could be used as a predictor of MACE in patients with ACS. The best cut-off value was 96.44 ng/µL, the diagnostic sensitivity was 75.71%, the specificity was 100%, and the area under the curve (AUC) was 0.931 (95% CI: 0.884–0.977, P<0.001).

Conclusions

Peripheral blood circRNAs are up-regulated about 3 fold in the peripheral blood of patients with ACS. Abnormal expression is an independent risk factor affecting MACE. Peripheral blood circRNAs can assist in clinical decision-making processes in patients with ACS.

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Most cited references 22

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Identification of High-Risk Plaques Destined to Cause Acute Coronary Syndrome Using Coronary Computed Tomographic Angiography and Computational Fluid Dynamics

Doyeon Hwang, Jonghanne Park, Jinlong Zhang … (2018)

The authors investigated the utility of noninvasive hemodynamic assessment in the identification of high-risk plaques that caused subsequent acute coronary syndrome (ACS).

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Circular RNA circDLGAP4 exerts neuroprotective effects via modulating miR-134-5p/CREB pathway in Parkinson’s disease

Zhong Feng, Li. Zhang, Sa Wang … (2019)

Parkinson's disease (PD) is a neurodegenerative disease which is characterized by the substantia nigra dopaminergic neurons denatured. Circular RNA (circRNA) DLGAP4 (circDLGAP4) was found to have neuroprotective effect. In this study, we aimed to investigate whether circDLGAP4 participates in the progression of PD. Here, our results showed that circDLGAP4 expression was decreased in MPTP-induced PD mouse model and MPP+-induced PD cell models. In vitro study revealed that circDLGAP4 could promote viability, reduce apoptosis, decrease mitochondrial damage, enhance autophagy and thereby attenuated the neurotoxic effects of MPP+ in SH-SY5Y and MN9D cells. Further research suggested that circDLGAP4 exerted its functions via regulating miR-134-5p. Moreover, we demonstrated that CREB was a target of miR-134-5p and CREB expression could be regulated by circDLGAP4/miR-134-5p axis. CircDLGAP4/miR-134-5p could also modulate the activation of CREB signaling and thereby influence the expression of CREB target genes including BDNF, Bcl-2 and PGC-1α in SH-SY5Y and MN9D cells. In all, our study identifies that circDLGAP4 exerts neuroprotective effects via modulating miR-134-5p/CREB pathway both in human and mouse.

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Circular RNA PIP5K1A promotes colon cancer development through inhibiting miR-1273a

Qu Zhang, Chi Zhang, Jian-Xin Ma … (2019)

BACKGROUND Circular RNAs (circRNAs) are considered to be highly stable due to the closed structure, which are predominately correlated with the development and progression of a wide variety of cancers. Colon cancer is one of the most common malignancies worldwide. A recent study demonstrated the upregulated expression of circPIP5K1A in non-small cell lung cancer. However, few studies have investigated the relationship between circ_0014130 level and colon cancer. Therefore, elucidating the underlying mechanisms of circPIP5K1A’s role may help with the identification of novel diagnostic and therapeutic targets for colon cancer. AIM To investigate the status of circPIP5K1A in colon cancers and its effects on the modulation of cancer development. METHODS The expression level of circPIP5K1A in tissue and serum samples from colon cancer patients, as well as human colonic cancer cell lines was detected by real-time quantitative reverse transcription-polymerase chain reaction. Following the transfection of specifically synthesized small interfering RNA (siRNA) into colon cell lines, we used Hoechst staining assay to measure the ratio of cell death in the absence of circPIP5K1A. Moreover, we also used the Transwell assay to assess the migratory function of colon cells overexpressing circPIP5K1A. Additionally, we employed a series of bioinformatics prediction programs to predict the potential of circPIP5K1A-targeted miRNAs and mRNAs. The miR-1273a vector was constructed, and then transfected with or without circPIP5K1A vector into colon cancer cells. Afterwards, the expression of activator protein 1 (AP-1), interferon regulating factor 4 (IRF-4), caudal type homeobox 2 (CDX-2), and zinc finger of the cerebellum 1 (Zic-1) was detected by western blotting. RESULTS CircPIP5K1A was significantly upregulated in colon cancer tissue relative to their adjacent normal tissues. Knockdown of circPIP5K1A in colon cancer cells impaired cell viability and suppressed cell invasion and migration, while enforced expression of circPIP5K1A exhibited the opposite effects on cell migration. Bioinformatics prediction program predicted that the association of circPIP5K1A with miR-1273a, as well as AP-1, IRF-4, CDX-2, and Zic-1. Subsequent studies showed that overexpression of circPIP5K1A augmented the expression of AP-1 but attenuated the expression of IRF-4, CDX-2, and Zic-1. Reciprocally, overexpression of miR-1273a abrogated the oncogenic function of circPIP5K1A in colon cancers. CONCLUSION Overall, our data demonstrate the oncogenic role of circPIP5K1A-miR-1273a axis in regulation of colon cancer development, which provides a novel insights into colon cancer pathogenesis.

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Author and article information

Journal

Journal ID (nlm-ta): J Thorac Dis

Journal ID (iso-abbrev): J Thorac Dis

Journal ID (publisher-id): JTD

Title: Journal of Thoracic Disease

Publisher: AME Publishing Company

ISSN (Print): 2072-1439

ISSN (Electronic): 2077-6624

Publication date (Print and electronic): April 2022

Publication date (Print): April 2022

Volume: 14

Issue: 4

Pages: 1139-1145

Affiliations

[1 ]deptDepartment of the Cardiovascular , the Fourth Affiliated Hospital of Anhui Medical University , Hefei, China;

[2 ]deptDepartment of Geriatric , Sanya Central Hospital (Hainan Third People’s Hospital) , Sanya, China;

[3 ]Department of Vascular Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia Hohhot , China

Author notes

Contributions: (I) Conception and design: C Chen, X Zhao; (II) Administrative support: X Xie; (III) Provision of study materials or patients: All authors; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

[#]

These authors contributed equally to this work.

Correspondence to: Xiaoliang Xie, MD. Attending Physician, Department of Vascular Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia Hohhot, China. Email: xxl812458@ 123456sina.com .

Article

Publisher ID: jtd-14-04-1139

DOI: 10.21037/jtd-22-253

PMC ID: 9096320

PubMed ID: 35572860

SO-VID: 328c0ffd-ac5a-416a-b1b7-ee6e50157bb6

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Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

Prognostic value of peripheral blood circular RNAs in patients with acute coronary syndrome

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Most cited references 22

Identification of High-Risk Plaques Destined to Cause Acute Coronary Syndrome Using Coronary Computed Tomographic Angiography and Computational Fluid Dynamics

Circular RNA circDLGAP4 exerts neuroprotective effects via modulating miR-134-5p/CREB pathway in Parkinson’s disease

Circular RNA PIP5K1A promotes colon cancer development through inhibiting miR-1273a

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