- Volume 17 Issue 6
Circulating DNA in Egyptian Women with Breast Cancer
- Ibrahim, Iman Hassan (Biochemistry Department, Faculty of Pharmacy for Girls -Al Azhar University) ;
- Kamel, Mahmoud M (Clinical Pathology Department, National Cancer Institute, Cairo University) ;
- Ghareeb, Mohamed (Department of Medical Oncology, National Cancer Institute, Cairo University)
- Published : 2016.06.01
The commonest cancer in Egyptian females occurs in the breast cfDNA is a non-invasive marker for tumor detetion and prognostic assessment in many types of cancer including breast cancer. This study aimed to assess the role of cfDNA and its fragmentation pattern in breast cancer prognosis and treatment response. Forty female patients with malignant breast tumors and a comparable group of healthy blood donors were enrolled prospectively. cfDNA levels and fragmentation patterns were investigated after cfDNA extraction, gel electrophoresis and gel analysis. The percentage of breast cancer patients positive for cfDNA (92.5%) was significantly higher than that of controls (55%). Also, mean concentration of cfDNA was significantly higher than in the control group (P<0.05). Most Her-2 positive patients had long cfDNA fragments, this being significant as compared to Her-2 negative patients (P<0.05). Metastasis was also positively linked to significantly higher cfDNA (P<0.05) and the mean cfDNA integrity index was significantly higher in non-responders compared to treatment responders (P<0.05). In conclusion, both qualitative and quantitative aspects of cfDNA and its different fragments in breast cancer patients could be related to prognosis, metastasis and treatment response. Long cfDNA fragments could be particularly useful for prediction purposes.
Breast cancer;circulating DNA;DNA fragments;treatment response
- Curigliano G, Disalvatore D, Esposito A, et al (2015). Risk of subsequent in situ and invasive breast cancer in human epidermal growth factor receptor 2-positive ductal carcinoma in situ. Ann Oncol, 26, 682-7. https://doi.org/10.1093/annonc/mdv013
- Dawson S-J, Tsui DWY, Murtaza M, et al (2013). Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med, 368, 1199-209. https://doi.org/10.1056/NEJMoa1213261
- Devonshire AS, Whale AS, Gutteridge A, et al (2014). Towards standardisation of cell-free DNA measurement in plasma: controls for extraction efficiency, fragment size bias and quantification. Anal Bioanal Chem, 406, 6499-512. https://doi.org/10.1007/s00216-014-7835-3
- Diehl F, Schmidt K, Choti MA, et al (2008). Circulating mutant DNA to assess tumor dynamics. Nat Med, 14, 985-90. https://doi.org/10.1038/nm.1789
- Ellinger J, Bastian PJ, Ellinger N, et al (2008). Apoptotic DNA fragments in serum of patients with muscle invasive bladder cancer: A prognostic entity. Cancer Letters, 264, 274-80. https://doi.org/10.1016/j.canlet.2008.01.038
- El Saghir NS, Khalil MK, Eid T, et al (2007). Trends in epidemiology and management of breast cancer in developing Arab countries: a literature and registry analysis. Int J Surg, 5, 225-33. https://doi.org/10.1016/j.ijsu.2006.06.015
- El-Shazly SF, Eid MA, El-Sourogy HA, Attia GF, Ezzat SA (2010). Evaluation of serum DNA integrity as a screening and prognostic tool in patients with hepatitis C virus-related hepatocellular carcinoma. Int J Biol Markers, 25, 79-86. https://doi.org/10.1177/172460081002500204
- Fang Y1, Chen Y, Yu L, et al (2013). Inhibition of breast cancer metastases by a novel inhibitor of TGF-receptor 1. J National Cancer Ins, 105, 47-58. https://doi.org/10.1093/jnci/djs485
- Ferlay J, Soerjomataram I, Dikshit R, et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer, 136, 359-86. https://doi.org/10.1002/ijc.29210
- Fleischhacker, M. and Schmidt, B (2007). Circulating nucleic acids (CNAs) and cancer-a survey. Biochim Biophys Acta, 1775, 181-232.
- Heras J, Dominguez C, Mata E, et al., A survey of tools for analysing DNA fingerprints. Briefings in bioinformatics. 2015, bbv016.
- Hashad D, Sorour A, Ghazal A, Talaat I (2012). Free circulating tumor DNA as a diagnostic marker for breast cancer. J Clin Lab. Anal, 26, 467-72.
- Huang ZH, Li LH, Hua D (2006). Quantitative analysis of plasma circulating DNA at diagnosis and during follow-up of breast cancer patients. Cancer Lett, 243, 64-70. https://doi.org/10.1016/j.canlet.2005.11.027
- Ibrahim AS, Khaled HM, Mikhail NNH, Baraka H, Kamel H (2014). Cancer incidence in Egypt: results of the national population-based cancer registry program. J Cancer Epidemiol, 437971, 18.
- Iqbal S, Vishnubhatla S, Raina V, et al (2015). Circulating cellfree DNA and its integrity as a prognostic marker for breast cancer. Springerplus, 17, 4-265.
- Kuo YB, Chen JS, Li YS,Chan EC (2014). Comparison of KRAS mutation analysis of primary tumors and matched circulating cell-free DNA in plasmas of patients with colorectal cancer. Clin Chim Acta, 433, 284-9. https://doi.org/10.1016/j.cca.2014.03.024
- Leszinski G, Lehner J, Gezer U and Holdenrieder S (2014). Increased DNA Integrity in colorectal cancer. In Vivo, 28, 299-303
- Lo YM, Chan KC, Sun H, et al (2010). Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci Transl Med, 2, 61-91.
- Madhavan D, Wallwiener M, Bents K, et al (2014). Plasma DNA integrity as a biomarker for primary and metastatic breast cancer and potential marker for early diagnosis. Breast Cancer Res Treat, 146, 163-74. https://doi.org/10.1007/s10549-014-2946-2
- Mead R, Duku M, Bhandari P, et al (2011). Circulating tumour markers can define patients with normal colons, benign polyps, and cancers. Br J Cancer, 105, 239-45. https://doi.org/10.1038/bjc.2011.230
- von Minckwitz G, Untch M, Nüesch E, et al (2011). Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neoadjuvant chemotherapy trials. Breast Cancer Res Treat, 125, 145-56. https://doi.org/10.1007/s10549-010-1228-x
- Mouliere F, Robert B, Arnau Peyrotte E, et al. (2011). High fragmentation characterizes tumour-derived circulating DNA. PloS One, 6, 23418. https://doi.org/10.1371/journal.pone.0023418
- Mouliere F, Rosenfeld N (2015). Circulating tumor-derived DNA is shorter than somatic DNA in plasma. Proc Natl Acad Sci U S A, 112, 3178-9. https://doi.org/10.1073/pnas.1501321112
- Ocana A, Diez-Gonzalez L, Garcia-Olmo DC, et al (2016). Circulating DNA and survival in solid tumors. Cancer Epidemiol Biomarkers Prev, 25, 399-406. https://doi.org/10.1158/1055-9965.EPI-15-0893
- Pal SK, Childs BH, Pegram M (2011). Triple negative breast cancer: unmet medical needs. Breast Cancer Res Treat, 125, 627-36. https://doi.org/10.1007/s10549-010-1293-1
- Pavel AB, Vasile (2012). PyElph - a software tool for gel images analysis and phylogenetics. BMC Bioinformatics, 13, 9. https://doi.org/10.1186/1471-2105-13-9
- Porter PL (2009). Global trends in breast cancer incidence and mortality. Salud P'ublica de M'exico, 51, 141-6. https://doi.org/10.1590/S0036-36342009000800003
- Steinman S, Wang J, Bourne P, et al (2007). Expression of cytokeratin markers, ER-alpha, PR, HER-2/neu, and EGFR in pure ductal carcinoma in situ (DCIS) and DCIS with coexisting invasive ductal carcinoma (IDC) of the breast. Ann Clin Lab Sci, 37, 127-34.
- Stirling D (2003). DNA extraction from plasma and serum. Methods in molecular biology, Vol. 226, PCR Protocols, Second Edition, 63.
- Stotzer OJ, Lehner J, Fersching-Gierlich D, Nagel D, Holdenrieder S (2014). Diagnostic relevance of plasma DNA and DNA integrity for breast cancer. Tumour Biol J Int Soc Onco-developmental Biol Med, 35, 1183-91. https://doi.org/10.1007/s13277-013-1158-4
- Tangvarasittichai O, Jaiwang W, Tangvarasittichai S (2015). The plasma DNA concentration as a potential breast cancer screening marker. Indian J Clin Biochem, 30, 55-8. https://doi.org/10.1007/s12291-013-0407-z