- Volume 16 Issue 18
DOI QR Code
Plasma Circulating Cell-free Nuclear and Mitochondrial DNA as Potential Biomarkers in the Peripheral Blood of Breast Cancer Patients
- Mahmoud, Enas H (Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University) ;
- Fawzy, Amal (Clinical and Chemical Pathology Department, National Cancer Institute, Cairo University) ;
- Ahmad, Omar K (Clinical and Chemical Pathology Department, National Cancer Institute, Cairo University) ;
- Ali, Amr M (General Surgery Department, Faculty of Medicine, Beni Swif University)
- Published : 2016.01.11
Background: In Egypt, breast cancer is estimated to be the most common cancer among females. It is also a leading cause of cancer-related mortality. Use of circulating cell-free DNA (ccf-DNA) as non-invasive biomarkers is a promising tool for diagnosis and follow-up of breast cancer (BC) patients. Objective: To assess the role of circulating cell free DNA (nuclear and mitochondrial) in diagnosing BC. Materials and Methods: Multiplex real time PCR was used to detect the level of ccf nuclear and mitochondrial DNA in the peripheral blood of 50 breast cancer patients together with 30 patients with benign lesions and 20 healthy controls. Laboratory investigations, histopathological staging and receptor studies were carried out for the cancer group. Receiver operating characteristic curves were used to evaluate the performance of ccf-nDNA and mtDNA. Results: The levels of both nDNA and mtDNA in the cancer group were significantly higher in comparison to the benign and the healthy control group. There was a statistically significant association between nDNA and mtDNA levels and well established prognostic parameters; namely, histological grade, tumour stage, lymph node status andhormonal receptor status. Conclusions: Our data suggests that nuclear and mitochondrial ccf-DNA may be used as non-invasive biomarkers in BC.
Breast cancer;ccf nuclear DNA;ccf mitochondrial DNA;diagnostic markers
- Bai RK, Chang J, Yeh KT, et al (2011). Mitochondrial DNA content varies with pathological characteristics of breast cancer. J Oncol, 2011, 10.
- Banin Hirata BK, Oda JM, Losi Guembarovski R, et al (2014) markers for breast cancer: prediction on tumor behavior. Dis Markers, 2014, 12.
- Beaver JA, Jelovac D1, Balukrishna S, et al (2014). Detection of cancer DNA in plasma of patients with early-stage breast cancer. Clin Cancer Res, 20, 2643-50. https://doi.org/10.1158/1078-0432.CCR-13-2933
- Board RE, Wardley AM, Dixon JM, et al (2010). Detection of PIK3CA mutations in circulating free DNA in patients with breast cancer. Breast Cancer Res Treat, 120, 461-7. https://doi.org/10.1007/s10549-010-0747-9
- Chiu TW, Young R, Chan LY, et al (2006). Plasma cell-free DNA as an indicator of severity of injury in burn patients. Clin Chem Lab Med, 44, 13-7.
- Cline SD (2012). Mitochondrial DNA damage and its consequences for mitochondrial gene expression. Biochim Biophys Acta, 1819, 979-91. https://doi.org/10.1016/j.bbagrm.2012.06.002
- Connolly JL (2006). Changes and problematic areas in interpretation of the AJCC Cancer Staging Manual, 6th Edition, for breast cancer. Arch Pathol Lab Med, 130, 287-91.
- Cormio A, Guerra F, Cormio G, et al (2012). Mitochondrial DNA content and mass increase in progression from normal to hyperplastic to cancer endometrium. BMC Res Notes, 5, 279. https://doi.org/10.1186/1756-0500-5-279
- Dawson SJ, Tsui DW, 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
- Deligezer U, Eralp Y, Akisik EE (2008). Size distribution of circulating cell-free DNA in sera of breast cancer patients in the course of adjuvant chemotherapy. Clin Chem Lab Med, 46, 311-7.
- 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
- Donnelly T, Al Khater A, Al-Bader S (2013). Arab women's breast cancer screening practices: a literature review. Asian Pac J Cancer Prev, 14, 4519-28. https://doi.org/10.7314/APJCP.2013.14.8.4519
- Dubey AK, Gupta U, Jain S (2015). Breast cancer statistics and prediction methodology: A systematic review and analysis. Asian Pac J Cancer Prev, 16, 4237-45. https://doi.org/10.7314/APJCP.2015.16.10.4237
- Elshimali YI, Khaddour H, Sarkissyan M, et al (2013). The clinical utilization of circulating cell free DNA (CCFDNA) in blood of cancer patients. Int J Mol Sci, 14, 18925-58. https://doi.org/10.3390/ijms140918925
- Gong B, Xue J, Yu J, et al (2012). Cell-free DNA in blood is a potential diagnostic biomarker of breast cancer. Oncol Lett, 3, 897-900.
- Hampton T (2007). Methods to detect circulating tumor DNA may help early diagnosis of cancer. JAMA, 298-1993-4.
- Jakupciak JP, Maragh S, Markowitz ME, et al (2008). Performance of mitochondrial DNA mutations detecting early stage cancer. BMC Cancer, 8, 285-96. https://doi.org/10.1186/1471-2407-8-285
- Kim MC, Cui FJ, Kim Y (2013). Hydrogen peroxide promotes epithelial to mesenchymal transition and stemness in human malignant mesothelioma cells. Asian Pac J Cancer Prev, 14, 3625-30. https://doi.org/10.7314/APJCP.2013.14.6.3625
- Kim MM, Clinger JD, Masayesva BG, et al (2004). Mitochondrial DNA quantity increases with histopathology grade in premalignant and malignant head and neck lesions. Clin Cancer Res, 10, 8512-5. https://doi.org/10.1158/1078-0432.CCR-04-0734
- Leon SA, Shapiro B, Sklaroff, DM, et al (1977). Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res, 37, 646-50.
- Nicolini C, Ens C, Cerutti T, et al (2013). Elevated level of Cell-Free plasma DNA is associated with advanced-stage breast cancer. Clin Chem Lab Med, 51, 277-8.
- Nourazarian AR, Kangari P, Salmaninejad A (2014). Roles of oxidative stress in the development and progression of breast cancer. Asian Pac J Cancer Prev, 15, 4745-51. https://doi.org/10.7314/APJCP.2014.15.12.4745
- Olsson E, Winter C, George A, et al (2015). Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease. EMBO Mol Med, 7, 1034-47 https://doi.org/10.15252/emmm.201404913
- Pinker K, Bogner W, Gruber S, et al (2011). Molecular Imaging in breast cancer-potential future aspects. Breast Care, 6, 110-9. https://doi.org/10.1159/000328275
- Poli G, Leonarduzzi G, Biasi F, Chiarpotto E (2004). Oxidative stress and cell signalling. Curr Med Chem, 11, 1163-82. https://doi.org/10.2174/0929867043365323
- Rainer TH, Wong KS, Lam W, et al (2007). Comparison of plasma beta globin DNA and S-100 protein concentrations in acute stroke. Clin Chim Acta, 376, 190-6. https://doi.org/10.1016/j.cca.2006.08.025
- Rani S, Clynes M, O'Driscoll L (2007). Detection of amplifiable mRNA extracellular to insulin producing cells: potential for predicting beta cell mass and function. Clin Chem, 53, 1936-44. https://doi.org/10.1373/clinchem.2007.087973
- Roth C, Pantel K, Muller V, et al (2011). Apoptosis-related deregulation of proteolytic activities and high serum levels of circulating nucleosomes and DNA in blood correlate with breast cancer progression. BMC Cancer, 11, 4. https://doi.org/10.1186/1471-2407-11-4
- Shapiro B, Chakrabarty M, Cohn EM, et al (1983).Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease. Cancer Res, 51, 2116-20.
- Shaw JA, Page K, Blighe K, (2012). Genomic analysis of circulating cell-free DNA infers breast cancer dormancy. Genome Res, 22, 220-31. https://doi.org/10.1101/gr.123497.111
- Tanaka H, Tsuda H, Nishimura S (2012). Role of circulating free alu DNA in endometrial cancer. Int J Gynecol Cancer, 22, 82-6. https://doi.org/10.1097/IGC.0b013e3182328c94
- Thyagarajan B, Wang R, Nelson H, Barcelo H, Koh WP, Yuan JM. (2013): Mitochondrial DNA copy number is prospectively associated with breast cancer risk. PLoS One, 8, 65968. https://doi.org/10.1371/journal.pone.0065968
- Uchida J, Kato K, Kukita Y, et al (2015). Diagnostic accuracy of noninvasive genotyping of EGFR in lung cancer patients by deep sequencing of plasma cell free DNA. Clin Chem, 61, 1191-6. https://doi.org/10.1373/clinchem.2015.241414
- Xia P, An HX, Dang CX, et al (2009). Decreased mitochondrial DNA content in blood samples of patients with stage I breast cancer. BMC Cancer, 9, 454. https://doi.org/10.1186/1471-2407-9-454
- Xia P, Radpour R, Zachariah R (2009). Simultaneous quantitative assessment of circulating cell-free mitochondrial and nuclear DNA by multiplex real-time PCR. Genet Mol Biol, 32, 20-4. https://doi.org/10.1590/S1415-47572009000100003
- Yadav N, Chandr D (2013). Mitochondrial DNA mutations and breast tumorigenesis. Biochim Biophys Acta, 1836, 336-44.
- Yildirim-Assaf S, Coumbos A, Hopfenmuller W, et al (2007). The prognostic significance of determining DNA content in breast cancer by DNA image cytometry: the role of high grade aneuploidy in node negative breast cancer. J Clin Pathol, 60, 649-55. https://doi.org/10.1136/jcp.2005.035550
- Yu M, Zhou Y, Shi Y, et al (2007). Reduced mitochondrial DNA copy number is correlated with tumor progression and prognosis in Chinese breast cancer patients. IUBMB Life, 59, 450-7. https://doi.org/10.1080/15216540701509955
- Zachariah RR, Schmid S, Buerki N, et al (2008). Levels of circulating cell-free nuclear and mitochondrial DNA in benign and malignant ovarian tumors. Obstet Gynecol, 112, 843-50. https://doi.org/10.1097/AOG.0b013e3181867bc0
- Zhong XY, Ladewig A, Schmid S, et al (2007). Elevated level of cell-free plasma DNA is associated with breast cancer. Arch Gynecol Obstet, 276, 327-31. https://doi.org/10.1007/s00404-007-0345-1
- Ziaei JZ, Sanaat Z, Asvadi I, et al (2013). Survival analysis of breast cancer patients in Northwest Iran. Asian Pac J Cancer Prev, 14, 39-42. https://doi.org/10.7314/APJCP.2013.14.1.39