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Review
. 2022 Feb 7;19(3):446-459.
doi: 10.7150/ijms.67094. eCollection 2022.

Diagnostic value of circRNAs as effective biomarkers in human cardiovascular disease: an updated meta-analysis

Zhexiao Zhang  1   2 , Runmin Guo  1 , Yuhui Wang  3 , Hairong Huang  2 , Jie Liu  2 , Chenfei Wang  2 , Hongfu Wu  4 , Tangbin Zou  1   2
Affiliations
Review

Diagnostic value of circRNAs as effective biomarkers in human cardiovascular disease: an updated meta-analysis

Zhexiao Zhang et al. Int J Med Sci. .

Abstract

Background: A growing body of literature has demonstrated that circular RNAs (circRNAs) are the potential biomarkers in human cardiovascular disease (CVD). Therefore, a meta-analysis based on current studies was accomplished to appraise the role of circRNAs in the diagnostic of CVD patients. Methods: Studies before October 30, 2021, were searched using PubMed, EMBASE, the Web of Science, and Cochrane Library. The diagnostic odds ratio (DOR) with a confidence interval (CI) of 95% was used to investigate the associations between circRNAs and CVDs. Results: A total of 27 eligible articles were selected, including 47 studies, with 6833 participants meeting the criteria standard constrain. The pooled overall sensitivity and specificity for circRNAs expression profile in differentiating CVD patients from controls (non-CVDs or healthy subjects) were 0.81 (95%CI 0.78-0.83) and 0.74 (95%CI 0.68-0.78), respectively; the overall positive likelihood ratio was 3.1 (95%CI 2.5-3.7); the negative likelihood ratio was 0.26 (95%CI 0.22-0.31); the overall diagnostic odds ratio corresponding to an area under the curve of 0.85 (95%CI 0.81-0.88) was 12 (95%CI 9-16). Subgroup analysis indicated that the serum rather than blood has higher diagnostic accuracy. Likewise, meta-regression analysis demonstrated that the specimen, detection method, sample size, and publication year were the main sources of heterogeneity. Sensitivity analysis and Deeks' funnel plot revealed that our results are relatively robust. Conclusions: Our evidence-based analysis results suggested that circRNAs provide higher diagnostic accuracy in the prediction of CVDs. Thus, circRNAs might be potential biomarkers in CVDs.

Keywords: biomarker; cardiovascular disease; circRNAs; diagnosis; meta-analysis.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
A flow diagram demonstrating the study selection process. The process of study selection including identification, screening, eligibility extraction, and inclusion steps were depicted in the flow diagram. Out of 220 records identified from three databases, 27 studies met the selection criteria.
Figure 2
Figure 2
Overall quality assessment of eligible studies by QUADAS-2 tool. A. Methodological quality summary (by study). B. Methodological quality graph (overall).
Figure 3
Figure 3
Forest plots for studies on overall circRNAs used in the diagnosis of CVDs among 27 studies included in the meta-analysis. (A) Sensitivity of circRNAs in diagnosis of CVDs and (B) specificity of circRNAs in diagnosis of CVDs.
Figure 4
Figure 4
Summary receiver operator characteristic curves (SROC) of circRNAs for the diagnosis of CVDs in overall population.
Figure 5
Figure 5
Sensitivity analysis of the result of the meta-analysis for CVDs.
Figure 6
Figure 6
Univariable meta-regression for sensitivity and specificity of circRNAs for diagnosis of CVDs.
Figure 7
Figure 7
Deeks' funnel plot evaluating the potential publication bias of the included studies.
Figure 8
Figure 8
Fagan's nomogram evaluating the overall value of circRNAs for diagnosis of CVDs. The pre-test probability was set at 20%.
See this image and copyright information in PMC

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References

    1. Global regional, national disability-adjusted life-years (DALYs) for 315 diseases injuries, healthy life expectancy (HALE) 1990-2015. a systematic analysis for the Global Burden of Disease Study 2015. Lancet (London, England) 2016;388(10053):1603–1658. - PMC - PubMed
    1. LaRocca TJ, Martens CR, Seals DR. Nutrition and other lifestyle influences on arterial aging. Ageing research reviews. 2017;39:106–119. - PMC - PubMed
    1. Mozaffarian D, Benjamin EJ, Go AS. et al. Executive Summary: Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016;133(4):447–454. - PubMed
    1. Viereck J, Thum T. Circulating Noncoding RNAs as Biomarkers of Cardiovascular Disease and Injury. Circulation research. 2017;120(2):381–399. - PubMed
    1. Beermann J, Piccoli MT, Viereck J, Thum T. Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches. Physiological reviews. 2016;96(4):1297–1325. - PubMed