Circulating Cell Free DNA as the Diagnostic Marker for Ovarian Cancer: A Systematic Review and Meta-Analysis

Abstract

BackgroundQuantitative analyses of circulating cell-free DNA (cfDNA) are potential methods for the detection of ovarian cancer. Many studies have evaluated these approaches, but the results were too inconsistent to be conclusive. This study is the first to systematically evaluate the accuracy of circulating cfDNA for the diagnosis of ovarian cancer by conducting meta-analysis.MethodsWe searched PubMed, Embase, Cochrane Library and the Chinese National Knowledge Infrastructure (CNKI) databases systematically for relevant literatures up to December 10, 2015. All analyses were conducted using Meta-DiSc1.4 and Stata 12.0 software. Sensitivity, specificity and other measures of accuracy of circulating cfDNA for the diagnosis of ovarian cancer were pooled. Meta-regression was performed to identify the sources of heterogeneity.ResultsThis meta-analysis included a total of 9 studies, including 462 ovarian cancer patients and 407 controls. The summary estimates for quantitative analysis of circulating cfDNA in ovarian cancer screen were as follows: sensitivity, 0.70 (95% confidence interval (CI), 0.65–0.74); specificity, 0.90 (95% CI, 0.87–0.93); positive likelihood ratio, 6.60 (95% CI, 3.90–11.17); negative likelihood ratio, 0.34 (95% CI, 0.25–0.47); diagnostic odds ratio, 26.05 (95% CI, 14.67–46.26); and area under the curve, 0.89 (95% CI, 0.83–0.95), respectively. There was no statistical significance for the evaluation of publication bias.ConclusionsCurrent evidence suggests that quantitative analysis of cfDNA has unsatisfactory sensitivity but acceptable specificity for the diagnosis of ovarian cancer. Further large-scale prospective studies are required to validate the potential applicability of using circulating cfDNA alone or in combination with conventional markers as diagnostic biomarker for ovarian cancer and explore potential factors that may influence the accuracy of ovarian cancer diagnosis.

Molecular Characterization of Epithelial Ovarian Cancer: Implications for Diagnosis and Treatment

“…Regarding temporal heterogeneity, some studies of high-grade ovarian serous cancer show that most clonal characteristics evident in recurrent or metastatic disease are present as subclonal populations within the primary tumor [40,49,52], although one study showed evidence of ongoing tumor evolution [51]. In this context, it is worth noting that assays for sequencing tumor cell-free circulating DNA from the bloodstream, while still evolving, have the potential to detect ovarian cancer at an early stage, to provide simultaneous genomic information on multiple tumor foci and to reveal ongoing changes in tumor genomic characteristics that occur following surgery and subsequent therapy, thereby circumventing many of the limitations imposed by direct sampling of heterogeneous tumors [54]. In addition, next-generation/high throughput sequencing studies of STIC specimens may provide an opportunity to uncover molecular processes involved in tumorigenesis and the development of tumor heterogeneity in the setting of high-grade serous ovarian cancer [7].…”

Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA

“…The discrepancies probably occur due to the different methods and pre-analytical conditions, the use of serum instead of plasma by some researchers and the different volumes of plasma/serum for cfDNA extraction. Many studies focused on the potential use of cfDNA as a diagnostic, prognostic and predictive biomarker in ovarian cancer and a recent meta-analysis by Zhou et al attempted to evaluate the role of cfDNA in ovarian cancer diagnosis [41]. An overview of the research studies on cfDNA in ovarian cancer is summarized in Table 2.…”

Amniotic fluid cell‐free DNA in preterm prelabor rupture of membranes

“…Currently, the assessment of cell‐free nDNA or mtDNA in different body fluids has gained attention in many areas of medicine . For example, in obstetrics, maternal blood cell‐free nDNA of fetal origin has been mainly used for noninvasive prenatal diagnosis .…”

“…[12][13][14][15][16][17][18] Currently, the assessment of cell-free nDNA or mtDNA in different body fluids has gained attention in many areas of medicine. [19][20][21][22][23] For example, in obstetrics, maternal blood cell-free nDNA of fetal origin has been mainly used for noninvasive prenatal diagnosis. 20 Additionally, its levels have been shown to be increased in various pregnancy complications such as miscarriage, preeclampsia, fetal growth restriction, and preterm delivery.…”

“…DISCUSSIONCurrently, cell-free nDNA and mtDNA in the plasma and serum are considered as novel biomarkers with possible clinical applications in prenatal diagnosis and oncology 20,22,23,[29][30][31]. However, their role in amniotic fluid with respect to the presence of infection-related and inflammatory complications in women with PPROM is unknown.…”