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. 2024 Jul 3:15:1413532.
doi: 10.3389/fmicb.2024.1413532. eCollection 2024.

Circulating free DNA as a diagnostic marker for echinococcosis: a systematic review and meta-analysis

Xiaoqin Luo #  1   2 , Ping Jiang #  1 , Jideng Ma  1 , Zian Li  2 , Jianwu Zhou  2 , Xiaoxing Wei  1 , Jide A  2 , Jinping Chai  2 , Yanke Lv  1 , Peng Cheng  1 , Chunhua Cao  1 , Xiangren A  1   2
Affiliations

Circulating free DNA as a diagnostic marker for echinococcosis: a systematic review and meta-analysis

Xiaoqin Luo et al. Front Microbiol. .

Abstract

Introduction: Echinococcosis is a chronic zoonotic disease caused by tapeworms of the genus Echinococcus. The World Health Organization (WHO) has identified encapsulated disease as one of 17 neglected diseases to be controlled or eliminated by 2050. There is no accurate, early, non-invasive molecular diagnostic method to detect echinococcosis. The feasibility of circulating free DNA as a diagnostic method for echinococcosis has yielded inconclusive results in a number of published studies. However, there has been no systematic evaluation to date assessing the overall performance of these assays. We report here the first meta-analysis assessing the diagnostic accuracy of cfDNA in plasma, serum, and urine for echinococcosis.

Methods: We systematically searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WeiPu databases up to 17 January 2024, for relevant studies. All analyses were performed using RevMan 5.3, Meta-DiSc 1.4, Stata 17.0, and R 4.3.1 software. The sensitivity, specificity, and other accuracy indicators of circulating free DNA for the diagnosis of echinococcosis were summarized. Subgroup analyses and meta-regression were performed to identify sources of heterogeneity.

Results: A total of 7 studies included 218 patients with echinococcosis and 214 controls (156 healthy controls, 32 other disease controls (non-hydatid patients), and 26 non-study-targeted echinococcosis controls were included). Summary estimates of the diagnostic accuracy of cfDNA in the diagnosis of echinococcosis were as follows: sensitivity (SEN) of 0.51 (95% CI: 0.45-0.56); specificity (SPE) of 0.99 (95% CI: 0.97-0.99); positive likelihood ratio (PLR) of 11.82 (95% CI: 6.74-20.74); negative likelihood ratio (NLR) of 0.57 (95% CI: 0.41-0.80); diagnostic ratio (DOR) of 36.63 (95% CI: 13.75-97.59); and area under the curve (AUC) value of 0.98 (95% CI: 0.96-1.00).

Conclusion: Existing evidence indicates that the combined specificity of circulating cfDNA for echinococcosis is high. However, the combined sensitivity performance is unsatisfactory due to significant inter-study heterogeneity. To strengthen the validity and accuracy of our findings, further large-scale prospective studies are required.Systematic review registrationThe systematic review was registered in the International Prospective Register of Systematic Reviews PROSPERO [CRD42023454158]. https://www.crd.york.ac.uk/PROSPERO/.

Keywords: circulating free DNA; diagnostic marker; echinococcosis; meta-analysis; systematic review.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart for screening studies of Echinococcosis.
Figure 2
Figure 2
Quality assessment of the studies selected for the meta-analysis (QUADAS-2).
Figure 3
Figure 3
Forest plot of sensitivity for quantitative analysis of circulating cell-free DNA in the diagnosis of Echinococcosis.
Figure 4
Figure 4
Forest plot of specificity for quantitative analysis of circulating cell-free DNA in the diagnosis of Echinococcosis.
Figure 5
Figure 5
Forest plot of estimate PLR for quantitative analysis of circulating cell-free DNA in the diagnosis of Echinococcosis.
Figure 6
Figure 6
Forest plot of estimate NLR for quantitative analysis of circulating cell-free DNA in the diagnosis of Echinococcosis.
Figure 7
Figure 7
Forest plot of DOR for quantitative analysis of circulating cell-free DNA in the diagnosis of Echinococcosis.
Figure 8
Figure 8
The SROC curve for quantitative analysis of circulating cell-free DNA in the diagnosis of Echinococcosis.
Figure 9
Figure 9
The Deeks’ funnel plot for the assessment of potential publication bias of the included studies.
Figure 10
Figure 10
Funnel plot for the analysis of the level of bias in meta-analytical data for cfDNA in Echinococcosis.
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