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 LU ; Sundquist, Jan LU ; Hedelius, Anna LU and Memon, Ashfaque A LU
(2020)
In Molecular Carcinogenesis
59(12).
p.1362-1370
- 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... (More)
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/μl; 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/μl; 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.
(Less)
- author
- Sundquist, Kristina
LU
; Sundquist, Jan
LU
; Hedelius, Anna
LU
and Memon, Ashfaque A
LU
- organization
- publishing date
- 2020-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular Carcinogenesis
- volume
- 59
- issue
- 12
- pages
- 9 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:85092341318
- pmid:33051887
- ISSN
- 1098-2744
- DOI
- 10.1002/mc.23261
- language
- English
- LU publication?
- yes
- additional info
- © 2020 The Authors. Molecular Carcinogenesis published by Wiley Periodicals LLC.
- id
- f8446865-f5ea-4555-af76-8f5927db1b31
- date added to LUP
- 2020-10-22 13:09:50
- date last changed
- 2024-04-03 15:52:24
@article{f8446865-f5ea-4555-af76-8f5927db1b31,
abstract = {{<p>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/μl; 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/μl; 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.</p>}},
author = {{Sundquist, Kristina and Sundquist, Jan and Hedelius, Anna and Memon, Ashfaque A}},
issn = {{1098-2744}},
language = {{eng}},
number = {{12}},
pages = {{1362--1370}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Molecular Carcinogenesis}},
title = {{Diagnostic potential of circulating cell-free nuclear and mitochondrial DNA for several cancer types and nonmalignant diseases : A study on suspected cancer patients}},
url = {{http://dx.doi.org/10.1002/mc.23261}},
doi = {{10.1002/mc.23261}},
volume = {{59}},
year = {{2020}},
}