Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors
Open accessAbstract
Background: With the aim to simplify cancer management, cancer research lately dedicated itself more and more to discover and develop non-invasive biomarkers. In this connection, circulating cell-free DNA (ccf DNA) seems to be a promising candidate. Altered levels of ccf nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) have been found in several cancer types and might have a diagnostic value. Methods: Using multiplex real-time PCR we investigated the levels of ccf nDNA and mtDNA in plasma samples from patients with malignant and benign breast tumors, and from healthy controls. To evaluate the applicability of plasma ccf nDNA and mtDNA as a biomarker for distinguishing between the three study-groups we performed ROC (Receiver Operating Characteristic) curve analysis. We also compared the levels of both species in the cancer group with clinicopathological parameters. Results: While the levels of ccf nDNA in the cancer group were significantly higher in comparison with the benign tumor group (P < 0.001) and the healthy control group (P < 0.001), the level of ccf mtDNA was found to be significantly lower in the two tumor-groups (benign: P < 0.001; malignant: P = 0.022). The level of ccf nDNA was also associated with tumor-size (<2 cm vs. >2 cm<5 cm; 2250 vs. 6658; Mann-Whitney-U-Test: P = 0.034). Using ROC curve analysis, we were able to distinguish between the breast cancer cases and the healthy controls using ccf nDNA as marker (cut-off: 1866 GE/ml; sensitivity: 81%; specificity: 69%; P < 0.001) and between the tumor group and the healthy controls using ccf mtDNA as marker (cut-off: 463282 GE/ml; sensitivity: 53%; specificity: 87%; P < 0.001). Conclusion: Our data suggests that nuclear and mitochondrial ccf DNA have potential as biomarkers in breast tumor management. However, ccf nDNA shows greater promise regarding sensitivity and specificity.
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Extracellular mtDNA is associated with various pathologies, including trauma, burn injury, cancer, and rheumatoid arthritis.
“As extracellular mtDNA is reportedly associated with various pathologies, including trauma25,26, burn injury27, cancer28 and rheumatoid arthritis17,29”
From Anti-mitochondrial autoantibodies in systemic lupus erythematosus and their association with disease manifestations (2019) · cites this paper as [28]
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- Authors
- Kohler, C., Radpour, R., Barekati, Z., Asadollahi, R., Bitzer, J., Wight, E., Bürki, N., Diesch, C., Holzgreve, W., & Zhong, X. Y.
- Affiliations
- University of Basel (CH)
- Kantonsspital Baselland (CH)
- University Medical Center Freiburg (DE)
- Corresponding author
- Zhong, Xiao Yan
- Venue
- Molecular Cancer
- Published
- 2009-11-17
- Volume
- 8
- Issue
- 1
- Pages
- 105-105
- ISSN
- 1476-4598 (ISSN-L)
- PMC
- PMC2780981
- OpenAlex
- W2171143590
- Cited by
- 215
- References
- 39
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 12 · 2023: 15 · 2022: 11 · 2021: 14 · 2020: 15 · 2019: 18 · 2018: 14 · 2017: 11 · 2016: 13 · 2015: 25 · 2014: 9 · 2013: 15 · 2012: 11
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Cancer (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (320000, 119722)
- Krebsliga Beider Basel
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Screening and Diagnostics
- Keywords
- cell-free DNA, cell-free mitochondrial DNA, breast cancer, benign breast tumors, plasma biomarkers, tumor size, sensitivity and specificity
- MeSH terms
- Breast Neoplasms, Cell Nucleus, Cell-Free System, Diagnosis, Differential, DNA, Mitochondrial, Female, Health, Humans, Lymph Nodes, Neoplasm Metastasis, Receptors, Estrogen, Receptors, Progesterone, ROC Curve, Biomarkers, Tumor, Cohort Studies, Case-Control Studies, Erb-b2 Receptor Tyrosine Kinases
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