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Diagnostic potential of circulating cell-free nuclear and mitochondrial DNA for several cancer types and nonmalignant diseases: A study on suspected cancer patients.

ABSTRACT: Circulating cell-free nuclear DNA (nDNA) has been implicated in individual cancer types with a diagnostic value; however, the role of cell-free mitochondrial DNA (mtDNA) in cancers is controversial. We aimed to investigate and compare the diagnostic potential of both nDNA and mtDNA for multiple cancers and to investigate their ability to distinguish multiple cancers from healthy controls and from nonmalignant diseases. We also investigated the prognostic value of both nDNA and mtDNA. The absolute copy number of circulating DNAs in suspected cancer patients (n?=?286) referred to a cancer diagnostic center and healthy controls (n?=?109) was quantified by droplet digital polymerase chain reaction. Among the suspected cancer patients, 66 (23%) were diagnosed with various cancers, 193 (67%) with nonmalignant diseases, and 27 (10%) with no active disease. Levels of nDNA were significantly higher in cancers (copies/?l; mean?±?SD, 21.0?±?14.2) as compared with nonmalignant diseases (15.2?±?10.0) and controls (9.3?±?4.1). In contrast, levels of mtDNA were significantly lower in cancers (copies/?l; mean?±?SD, 68,557?±?66,663) and nonmalignant diseases (60,174?±?55,831) as compared with controls (98,714?±?77,789). Receiver operating curve analysis showed that nDNA not only could distinguish multiple cancers from controls (area under curve [AUC]?=?0.78; 95% confidence interval [CI]?=?0.70-0.86) but also from nonmalignant diseases (AUC?=?0.68; 95% CI?=?0.59-0.76). However, mtDNA could only differentiate cancers from controls (AUC?=?0.65; 95% CI?=?0.56-0.73). Higher levels of nDNA were also associated with increased mortality in the cancer patients (hazard ratio?=?2.3; 95% CI?=?1.1-4.7). Circulating cell-free nDNA, but not the mtDNA, could distinguish multiple cancers from nonmalignant diseases and was associated with poor survival of cancer patients.

SUBMITTER: Sundquist K

PROVIDER: S-EPMC7702094 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Diagnostic potential of circulating cell-free nuclear and mitochondrial DNA for several cancer types and nonmalignant diseases: A study on suspected cancer patients.

Sundquist Kristina K Sundquist Jan J Hedelius Anna A Memon Ashfaque A AA

Molecular carcinogenesis 20201013 12

Circulating cell-free nuclear DNA (nDNA) has been implicated in individual cancer types with a diagnostic value; however, the role of cell-free mitochondrial DNA (mtDNA) in cancers is controversial. We aimed to investigate and compare the diagnostic potential of both nDNA and mtDNA for multiple cancers and to investigate their ability to distinguish multiple cancers from healthy controls and from nonmalignant diseases. We also investigated the prognostic value of both nDNA and mtDNA. The absolut ...[more]

PMID: 33051887

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Project description:BackgroundBreast cancer (BC) is the most frequently diagnosed cancer among women. Numerous studies explored cell-free circulating microRNAs as diagnostic biomarkers of BC. As inconsistent and rarely intersecting microRNA panels have been reported thus far, we aim to evaluate the overall diagnostic performance as well as the sources of heterogeneity between studies.MethodsBased on the search of three online search engines performed up to March 21st 2022, 56 eligible publications that investigated diagnostic circulating microRNAs by utilizing Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) were obtained. Primary studies' potential for bias was evaluated with the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). A bivariate generalized linear mixed-effects model was applied to obtain pooled sensitivity and specificity. A novel methodology was utilized in which the sample and study models' characteristics were analysed to determine the potential preference of studies for sensitivity or specificity.ResultsPooled sensitivity and specificity of 0.85 [0.81-0.88] and 0.83 [0.79-0.87] were obtained, respectively. Subgroup analysis showed a significantly better performance of multiple (sensitivity: 0.90 [0.86-0.93]; specificity: 0.86 [0.80-0.90]) vs single (sensitivity: 0.82 [0.77-0.86], specificity: 0.83 [0.78-0.87]) microRNA panels and a comparable pooled diagnostic performance between studies using serum (sensitivity: 0.87 [0.81-0.91]; specificity: 0.83 [0.78-0.87]) and plasma (sensitivity: 0.83 [0.77-0.87]; specificity: 0.85 [0.78-0.91]) as specimen type. In addition, based on bivariate and univariate analyses, miRNA(s) based on endogenous normalizers tend to have a higher diagnostic performance than miRNA(s) based on exogenous ones. Moreover, a slight tendency of studies to prefer specificity over sensitivity was observed.ConclusionsIn this study the diagnostic ability of circulating microRNAs to diagnose BC was reaffirmed. Nonetheless, some subgroup analyses showed between-study heterogeneity. Finally, lack of standardization and of result reproducibility remain the biggest issues regarding the diagnostic application of circulating cell-free microRNAs.

Dataset Information

Diagnostic potential of circulating cell-free nuclear and mitochondrial DNA for several cancer types and nonmalignant diseases: A study on suspected cancer patients.

Publications

Diagnostic potential of circulating cell-free nuclear and mitochondrial DNA for several cancer types and nonmalignant diseases: A study on suspected cancer patients.

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