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Published in: Tumor Biology 6/2016

01-06-2016 | Original Article

Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer

Authors: Azza M. Kamel, Salwa Teama, Amal Fawzy, Mervat El Deftar

Published in: Tumor Biology | Issue 6/2016

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Abstract

Plasma DNA integrity index is increased in various malignancies including breast cancer, the most common cancer in women worldwide; early detection is crucial for successful treatment. Current screening methods fail to detect many cases of breast cancer at an early stage. In this study, we evaluated the level of plasma DNA integrity index in 260 females (95 with breast cancer, 95 with benign breast lesions, and 70 healthy controls) to verify its potential value in discriminating malignant from benign breast lesions. The criteria of the American Joint Committee on Cancer were used for staging of breast cancer patients. DNA integrity index was measured by real-time PCR. DNA integrity index was significantly higher in breast cancer than in benign breast patients and healthy subjects (P = <0.001). DNA integrity index is correlated with TNM stage. Given 100 % specificity, the highest sensitivity achieved in detecting cancer group was 85.3 % at 0.55 DNA integrity index cutoff. In conclusion, the plasma DNA integrity index may be a promising molecular diagnostic marker of malignancy in breast lesions.
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Literature
1.
go back to reference Abdulrahman Jnr GO, Rahman GA. Epidemiology of breast cancer in Europe and Africa. Review article. J Cancer Epidemiol. 2012;2012, 915610. doi:10.1155/2012/915610. Abdulrahman Jnr GO, Rahman GA. Epidemiology of breast cancer in Europe and Africa. Review article. J Cancer Epidemiol. 2012;2012, 915610. doi:10.​1155/​2012/​915610.
3.
go back to reference Omar S, Khaled H, Gaafar R, Zekry AR, Eissa S, El-Khatib O. Breast cancer in Egypt: a review of disease presentation and detection strategies. East Mediterr Health J = La Revue de Santé de la Méditerranée. 2003;9:448–63. Omar S, Khaled H, Gaafar R, Zekry AR, Eissa S, El-Khatib O. Breast cancer in Egypt: a review of disease presentation and detection strategies. East Mediterr Health J = La Revue de Santé de la Méditerranée. 2003;9:448–63.
4.
go back to reference Mandel P, Metais P. Circulating nucleic acid. Acad Sci Paris. 1948;142:241–3. Mandel P, Metais P. Circulating nucleic acid. Acad Sci Paris. 1948;142:241–3.
5.
go back to reference Wang BG, Huang HY, Chen YC, Bristow RE, Kassauei K, Cheng CC, et al. Increased plasma DNA integrity in cancer patients. Cancer Res. 2003;63:3966–8.PubMed Wang BG, Huang HY, Chen YC, Bristow RE, Kassauei K, Cheng CC, et al. Increased plasma DNA integrity in cancer patients. Cancer Res. 2003;63:3966–8.PubMed
6.
go back to reference Leon SA, Shapiro B, Sklaroff DM, Yaros MJ. Free DNA in serum of cancer patients and the effect of therapy. Cancer Res. 1977;37:646–50.PubMed Leon SA, Shapiro B, Sklaroff DM, Yaros MJ. Free DNA in serum of cancer patients and the effect of therapy. Cancer Res. 1977;37:646–50.PubMed
7.
go back to reference Shapiro B, Chakrabarty M, Cohn EM, Leon SA. Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease. Cancer. 1983;51:2116–20.CrossRefPubMed Shapiro B, Chakrabarty M, Cohn EM, Leon SA. Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease. Cancer. 1983;51:2116–20.CrossRefPubMed
8.
go back to reference Anker P, Stroun M. Circulating DNA in plasma or serum. Medicina (B Aires). 2000;60(5 Pt 2):699–702. Anker P, Stroun M. Circulating DNA in plasma or serum. Medicina (B Aires). 2000;60(5 Pt 2):699–702.
9.
go back to reference Gormally E, Caboux E, Vineis P, Hainaut P. Circulating free DNA in plasma/serum as biomarker of carcinogenesis. Practical aspects and biological significance. Mutat Res. 2007;635:105–17.CrossRefPubMed Gormally E, Caboux E, Vineis P, Hainaut P. Circulating free DNA in plasma/serum as biomarker of carcinogenesis. Practical aspects and biological significance. Mutat Res. 2007;635:105–17.CrossRefPubMed
12.
go back to reference Giacona MB, Ruben GC, Iczkowski KA, Roos TB, Porter DM, Sorenson GD. Cell free DNA in human blood plasma, length measurements in patients with pancreatic cancer and healthy controls. Pancreas. 1998;17:89–97.CrossRefPubMed Giacona MB, Ruben GC, Iczkowski KA, Roos TB, Porter DM, Sorenson GD. Cell free DNA in human blood plasma, length measurements in patients with pancreatic cancer and healthy controls. Pancreas. 1998;17:89–97.CrossRefPubMed
13.
go back to reference Bargmann CI, Hung MC, Weinberg RA. The neu oncogene encodes an epidermal growth factor related protein. Nature. 1986;319(22):6–30. Bargmann CI, Hung MC, Weinberg RA. The neu oncogene encodes an epidermal growth factor related protein. Nature. 1986;319(22):6–30.
14.
go back to reference Pupa SM, Ménard S, Morelli D, Pozzi B, De Palo G, Colnaghi MI. The extracellular domain of the c-erbB-2 oncoprotein is released from tumor cells by proteolytic cleavage. Oncogene. 1983;8:2917–23. Pupa SM, Ménard S, Morelli D, Pozzi B, De Palo G, Colnaghi MI. The extracellular domain of the c-erbB-2 oncoprotein is released from tumor cells by proteolytic cleavage. Oncogene. 1983;8:2917–23.
15.
go back to reference Ross JS, Fletcher JA, Linette GP, Stec J, Clark E, Ayers M, et al. The Her-2/neu gene and protein in breast cancer: biomarker and target of therapy. Oncologist. 2003;8:307–25.CrossRefPubMed Ross JS, Fletcher JA, Linette GP, Stec J, Clark E, Ayers M, et al. The Her-2/neu gene and protein in breast cancer: biomarker and target of therapy. Oncologist. 2003;8:307–25.CrossRefPubMed
16.
go back to reference Anker P, Mulcahy H, Chen XQ, Stroun M. Detection of circulating tumour DNA in the blood (plasma/serum) of cancer patients. Cancer Metastasis Rev. 1999;18:65–73.CrossRefPubMed Anker P, Mulcahy H, Chen XQ, Stroun M. Detection of circulating tumour DNA in the blood (plasma/serum) of cancer patients. Cancer Metastasis Rev. 1999;18:65–73.CrossRefPubMed
17.
go back to reference Allen D, Butt A, Cahill D, Wheeler M, Popert R, Swaminathan R. Role of cell-free plasma DNA as a diagnostic marker for prostate cancer. Ann N Y Acad Sci. 2004;1022:76–80.CrossRefPubMed Allen D, Butt A, Cahill D, Wheeler M, Popert R, Swaminathan R. Role of cell-free plasma DNA as a diagnostic marker for prostate cancer. Ann N Y Acad Sci. 2004;1022:76–80.CrossRefPubMed
18.
go back to reference Jung K, Stephan C, Lewandowski M, Klotzek S, Jung M, Kristiansen G, et al. Increased cell-free DNA in plasma of patients with metastatic spread in prostate cancer. Cancer Lett. 2004;205:173–80.CrossRefPubMed Jung K, Stephan C, Lewandowski M, Klotzek S, Jung M, Kristiansen G, et al. Increased cell-free DNA in plasma of patients with metastatic spread in prostate cancer. Cancer Lett. 2004;205:173–80.CrossRefPubMed
19.
go back to reference Boddy JL, Gal S, Malone PR, Harris AL, Wainscoat JS. Prospective study of quantitation of plasma DNA levels in the diagnosis of malignant versus benign prostate disease. Clin Cancer Res. 2005;11:1394–9.CrossRefPubMed Boddy JL, Gal S, Malone PR, Harris AL, Wainscoat JS. Prospective study of quantitation of plasma DNA levels in the diagnosis of malignant versus benign prostate disease. Clin Cancer Res. 2005;11:1394–9.CrossRefPubMed
20.
go back to reference Ahlquist DA, Skoletsky JE, Boynton KA, Harrington JJ, Mahoney DW, Pierceall WE, et al. Colorectal cancer screening by detection of altered human DNA in stool: feasibility of a multitarget assay panel. Gastroenterology. 2000;119:1219–27.CrossRefPubMed Ahlquist DA, Skoletsky JE, Boynton KA, Harrington JJ, Mahoney DW, Pierceall WE, et al. Colorectal cancer screening by detection of altered human DNA in stool: feasibility of a multitarget assay panel. Gastroenterology. 2000;119:1219–27.CrossRefPubMed
21.
go back to reference Sorenson GD, Pribish DM, Valone FH, Memoli VA, Bzik DJ, Yao SL. Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cancer Epidemiol Biomarkers Prev. 1994;3:67–71.PubMed Sorenson GD, Pribish DM, Valone FH, Memoli VA, Bzik DJ, Yao SL. Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cancer Epidemiol Biomarkers Prev. 1994;3:67–71.PubMed
22.
go back to reference Vasioukhin V, Anker P, Maurice P, Lyautey J, Lederrey C, Stroun M. Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia. Br J Haematol. 1994;86:774–9.CrossRefPubMed Vasioukhin V, Anker P, Maurice P, Lyautey J, Lederrey C, Stroun M. Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia. Br J Haematol. 1994;86:774–9.CrossRefPubMed
23.
go back to reference Jiajia Y, Guohao G, Shaoqing J. Recent advances in clinical applications of circulating cell-free DNA integrity. Lab Med. 2014;45:6–12.CrossRef Jiajia Y, Guohao G, Shaoqing J. Recent advances in clinical applications of circulating cell-free DNA integrity. Lab Med. 2014;45:6–12.CrossRef
24.
go back to reference Boynton KA, Summerhayes IC, Ahlquist DA, Shuber AP. DNA integrity as a potential marker for stool-based detection of colorectal cancer. Clin Chem. 2003;49:1058–65.CrossRefPubMed Boynton KA, Summerhayes IC, Ahlquist DA, Shuber AP. DNA integrity as a potential marker for stool-based detection of colorectal cancer. Clin Chem. 2003;49:1058–65.CrossRefPubMed
25.
go back to reference Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 2001;61:1659–65.PubMed Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD, et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 2001;61:1659–65.PubMed
26.
go back to reference Chen XQ, Stroun M, Magnenat JL, Nicod LP, Kurt AM, Lyautey J, et al. Microsatellite alterations in plasma DNA of small cell lung cancer patients. Nat Med. 1996;2:1033–5.CrossRefPubMed Chen XQ, Stroun M, Magnenat JL, Nicod LP, Kurt AM, Lyautey J, et al. Microsatellite alterations in plasma DNA of small cell lung cancer patients. Nat Med. 1996;2:1033–5.CrossRefPubMed
27.
go back to reference Nawroz H, Koch W, Anker P, Stroun M, Sidransky D. Microsatellite alterations in serum DNA of head and neck cancer patients. Nat Med. 1996;2:1035–7.CrossRefPubMed Nawroz H, Koch W, Anker P, Stroun M, Sidransky D. Microsatellite alterations in serum DNA of head and neck cancer patients. Nat Med. 1996;2:1035–7.CrossRefPubMed
28.
go back to reference Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, Herman JG. Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Res. 1999;59:67–70.PubMed Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, Herman JG. Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. Cancer Res. 1999;59:67–70.PubMed
29.
go back to reference Maebo A. Plasma DNA level as a tumor marker in primary lung cancer. Nihon Kyobu Shikkan Gakkai Zasshi. 1990;28:1085–91 (Abstract).PubMed Maebo A. Plasma DNA level as a tumor marker in primary lung cancer. Nihon Kyobu Shikkan Gakkai Zasshi. 1990;28:1085–91 (Abstract).PubMed
30.
go back to reference Umetani N, Giuliano AE, Hiramatsu SH, Amersi F, Nakagawa T, Martino S, et al. Prediction of breast tumor progression by integrity of free circulating DNA in serum. J Clin Oncol. 2006;24:4270–6.CrossRefPubMed Umetani N, Giuliano AE, Hiramatsu SH, Amersi F, Nakagawa T, Martino S, et al. Prediction of breast tumor progression by integrity of free circulating DNA in serum. J Clin Oncol. 2006;24:4270–6.CrossRefPubMed
31.
go back to reference Chang H-W, Lee SM, Goodman SN, Singer G, Cho S, Sokoll LJ, et al. Assessment of plasma DNA levels, allelic imbalance, and CA 125 as diagnostic tests for cancer. J Natl Cancer Inst. 2002;94:1697–703.CrossRefPubMed Chang H-W, Lee SM, Goodman SN, Singer G, Cho S, Sokoll LJ, et al. Assessment of plasma DNA levels, allelic imbalance, and CA 125 as diagnostic tests for cancer. J Natl Cancer Inst. 2002;94:1697–703.CrossRefPubMed
32.
go back to reference Agassi R, Czeiger D, Shaked G, Avriel A, Sheynin J, Lavrnkov K, et al. Measurement of circulating cell-free DNA levels by a simple fluorescent test in patients with breast cancer. Am J Clin Pathol. 2015;143(1):18–24. doi:10.1309/AJCPI5YHG0OGFAHM.CrossRefPubMed Agassi R, Czeiger D, Shaked G, Avriel A, Sheynin J, Lavrnkov K, et al. Measurement of circulating cell-free DNA levels by a simple fluorescent test in patients with breast cancer. Am J Clin Pathol. 2015;143(1):18–24. doi:10.​1309/​AJCPI5YHG0OGFAHM​.CrossRefPubMed
33.
go back to reference El-Shazly SF, Eid MA, El-Sourogy HA, Attia GF, Ezzat SA. Evaluation of serum DNA integrity as a screening and prognostic tool in patients with hepatitis C virus-related hepatocellular carcinoma. Int J Biol Markers. 2010;25:79–86.PubMed El-Shazly SF, Eid MA, El-Sourogy HA, Attia GF, Ezzat SA. Evaluation of serum DNA integrity as a screening and prognostic tool in patients with hepatitis C virus-related hepatocellular carcinoma. Int J Biol Markers. 2010;25:79–86.PubMed
36.
go back to reference Kamel AM, Teama S, Fawzy A, El Deftar M. Increased plasma DNA integrity index in breast cancer patients. AACC. 2011; Abstract 09. Kamel AM, Teama S, Fawzy A, El Deftar M. Increased plasma DNA integrity index in breast cancer patients. AACC. 2011; Abstract 09.
37.
go back to reference Sozzi G, Conte D, Mariani L, Lo Vullo S, Roz L, Lombardo C, et al. Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients. Cancer Res. 2001;61:4675–8.PubMed Sozzi G, Conte D, Mariani L, Lo Vullo S, Roz L, Lombardo C, et al. Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients. Cancer Res. 2001;61:4675–8.PubMed
38.
go back to reference Hanley R, Rieger-Christ KM, Canes D, Emara NR, Shuber AP, Boynton KA, et al. DNA integrity assay: a plasma-based screening tool for the detection of prostate cancer. Clin Cancer Res. 2006;12:4569–74.CrossRefPubMed Hanley R, Rieger-Christ KM, Canes D, Emara NR, Shuber AP, Boynton KA, et al. DNA integrity assay: a plasma-based screening tool for the detection of prostate cancer. Clin Cancer Res. 2006;12:4569–74.CrossRefPubMed
42.
go back to reference Sriram KB, Relan V, Clarke BE, Duhig EE, Windsor MN, Matar KS, et al. Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including mesotheliomas. BMC Cancer. 2012;12:428. doi:10.1186/1471-2407-12-428.CrossRefPubMed Sriram KB, Relan V, Clarke BE, Duhig EE, Windsor MN, Matar KS, et al. Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including mesotheliomas. BMC Cancer. 2012;12:428. doi:10.​1186/​1471-2407-12-428.CrossRefPubMed
44.
go back to reference Madhavan D, Wallwiener M, Bents K, Zucknick M, Nees J, Schott S, et al. Plasma DNA integrity as a biomarker for primary and metastatic breast cancer and potential marker for early diagnosis. Breast Cancer Res Treat. 2014;146:163–73. doi:10.1007/s10549-014-2946-2.CrossRefPubMed Madhavan D, Wallwiener M, Bents K, Zucknick M, Nees J, Schott S, et al. Plasma DNA integrity as a biomarker for primary and metastatic breast cancer and potential marker for early diagnosis. Breast Cancer Res Treat. 2014;146:163–73. doi:10.​1007/​s10549-014-2946-2.CrossRefPubMed
47.
go back to reference Ellinger J, Bastian PJ, Haan KI, Heukamp LC, Buettner R, Fimmers R, et al. Noncancerous PTGS2 DNA fragments of apoptotic origin in sera of prostate cancer patients qualify as diagnostic and prognostic indicators. Int J Cancer. 2008;122:138–43.CrossRefPubMed Ellinger J, Bastian PJ, Haan KI, Heukamp LC, Buettner R, Fimmers R, et al. Noncancerous PTGS2 DNA fragments of apoptotic origin in sera of prostate cancer patients qualify as diagnostic and prognostic indicators. Int J Cancer. 2008;122:138–43.CrossRefPubMed
Metadata
Title
Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer
Authors
Azza M. Kamel
Salwa Teama
Amal Fawzy
Mervat El Deftar
Publication date
01-06-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 6/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4624-3

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