Issue
Cell-free DNA as a biomarker for colorectal cancer: a retrospective analysis in patients before and after surgery
Corresponding Author(s) : Lingxiang Chen
Cellular and Molecular Biology,
Vol. 66 No. 2: Issue 2
Abstract
This study was aimed at investigating the potential of cell-free DNA (cfDNA) as a biomarker for colorectal cancer prognosis. Sixty patients with colorectal cancer who had not undergone surgery were enrolled as study group. Their peripheral blood samples were collected, and peripheral blood of 30 healthy volunteers (control) was collected. The cfDNA concentration and integrity were determined using q-PCR so as to ascertain if cfDNA was associated with clinical presentations of the disease. Then, the specificities and sensitivities of cfDNA, CFA and CA199 were determined with ROC curve. The level and integrity of cfDNA in patients with colorectal cancer before surgery were significantly higher than those in patients with colorectal cancer after surgery, and cfDNA concentration of colorectal cancer patients after surgery was also significantly higher than that in healthy control group. However, the integrity was not significantly different from that of control group. There was a significant correlation between cfDNA concentration and TNM stage, differentiation degree and CEA expression, while cfDNA integrity was significantly correlated with TNM stage and degree of differentiation. Moreover, specificity and sensitivity of cfDNA concentration and integrity were higher than those of CEA and CA199. The TNM stage and cfDNA concentration were independent risk factors for progression-free survival (PFS) in colorectal cancer patients. In conclusion, cfDNA concentration and integrity were more sensitive and specific than traditional tumor markers (CA199, CEA). Thus, changes in cfDNA changes can be effectively used to determine the prognosis of postoperative colorectal cancer patients.
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- Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: 359-386.
- Nishihara R, Wu K, Lochhead P, Morikawa T, Liao X, Qian ZR, et al. Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med 2013; 369: 1095-1105.
- Franchi M, Barni S, Tagliabue G, Ricci P, Mazzucco W, Tumino R, et al. Effectiveness of First-Line Bevacizumab in Metastatic Colorectal Cancer: The Observational Cohort Study GRETA. Oncologist 2018; 24: 358-365.
- Tsavaris N, Mavragani CP, Pikazis D. Rheumatoid arthritis: correlation between rheumatoid factor levels and CA-125 tumour marker elevation. Ann Rheum Dis 2007; 66: 980.
- Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol 2013; 10: 472-484.
- Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 2011; 11: 426-437.
- Leon SA, Shapiro B, Sklaroff DM, Yaros MJ. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 1977; 37: 646-650.
- Spindler KL, Sorensen MM, Pallisgaard N, Andersen RF, Havelund BM, Ploen J, et al. Phase II trial of temsirolimus alone and in combination with irinotecan for KRAS mutant metastatic colorectal cancer: outcome and results of KRAS mutational analysis in plasma. Acta Oncol 2013; 52: 963-970.
- Spindler KL, Pallisgaard N, Vogelius I, Jakobsen A. Quantitative cell-free DNA, KRAS, and BRAF mutations in plasma from patients with metastatic colorectal cancer during treatment with cetuximab and irinotecan. Clin Cancer Res 2012; 18:1177-1185.
- Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med 2008; 14: 985-990.
- Brenner H. Colorectal cancer. Lancet 2014; 383: 1490-1502.
- Gorgannezhad L, Umer M, Islam MN, Nguyen NT, Shiddiky MJA. Circulating tumor DNA and liquid biopsy: opportunities, challenges, and recent advances in detection technologies. Lab Chip 2018; 18: 1174-1196.
- Pinzani P, Salvianti F, Zaccara S, Massi D, De Giorgi V, Pazzagli M, et al. Circulating cell-free DNA in plasma of melanoma patients: qualitative and quantitative considerations. Clin Chim Acta 2011; 412: 2141-2145.
- 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: 3966-3968.
- Chen K, Zhang H, Zhang LN, Ju SQ, Qi J, Huang DF, et al. Value of circulating cell-free DNA in diagnosis of hepatocelluar carcinoma. World J Gastroenterol 2013; 19: 3143-3149.
- Frattini M, Gallino G, Signoroni S, Balestra D, Battaglia L, Sozzi G, et al. Quantitative analysis of plasma DNA in colorectal cancer patients: a novel prognostic tool. Ann N Y Acad Sci 2006; 1075: 185-190.
- Laufer-Geva S, Rozenblum AB, Twito T, Grinberg R, Dvir A, Soussan-Gutman L, et al. The Clinical Impact of Comprehensive Genomic Testing of Circulating Cell-Free DNA in Advanced Lung Cancer. J Thorac Oncol 2018; 13: 1705-1716.
- Zhou S, Xu B, Qi L, Zhu D, Liu B, Wei J. Next-generation sequencing reveals mutational accordance between cell-free DNA from plasma, malignant pleural effusion and ascites and directs targeted therapy in a gastric cancer patient. Cancer Biol Ther 2018; 20: 15-20.
- Hsieh CC, Hsu HS, Chang SC, Chen YJ. Circulating Cell-Free DNA Levels Could Predict Oncological Outcomes of Patients Undergoing Esophagectomy for Esophageal Squamous Cell Carcinoma. Int J Mol Sci 2016; 17: 12.
- Kamel AM, Teama S, Fawzy A, EI Deftar M. Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer. Tumour Biol 2016; 37: 7565-7572.
- Huang A, Zhang X, Zhou SL, Cao Y, Huang XW, Fan J, et al. Plasma Circulating Cell-free DNA Integrity as a Promising Biomarker for Diagnosis and Surveillance in Patients with Hepatocellular Carcinoma. J Cancer 2016; 7: 1798-1803.
- Yoruker EE, í–zgür E, Keskin M, Dalay N, Holdenrieder S, Gezer U. Assessment of circulating serum DNA integrity in colorectal cancer patients. Anticancer Res 2015; 35: 2435-2440.
- Cheng J, Cuk K, Heil J, Golatta M, Schott S, Sohn C, et al. Cell-free circulating DNA integrity is an independent predictor of impending breast cancer recurrence. Oncotarget 2017; 8: 54537-54547.
- Aarthy R, Mani S, Velusami S, Sundarsingh S, Rajkumar T. Role of Circulating Cell-Free DNA in Cancers. Mol Diagn Ther 2015; 19: 339-350.
- Yang J, Cheng L, Zhang J, Chen L, Wang D, Guo X, et al. Predictive value of circulating cell-free DNA in the survival of breast cancer patients: A systemic review and meta-analysis. Med (Baltimore) 2018; 97: 11417.
References
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: 359-386.
Nishihara R, Wu K, Lochhead P, Morikawa T, Liao X, Qian ZR, et al. Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med 2013; 369: 1095-1105.
Franchi M, Barni S, Tagliabue G, Ricci P, Mazzucco W, Tumino R, et al. Effectiveness of First-Line Bevacizumab in Metastatic Colorectal Cancer: The Observational Cohort Study GRETA. Oncologist 2018; 24: 358-365.
Tsavaris N, Mavragani CP, Pikazis D. Rheumatoid arthritis: correlation between rheumatoid factor levels and CA-125 tumour marker elevation. Ann Rheum Dis 2007; 66: 980.
Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol 2013; 10: 472-484.
Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 2011; 11: 426-437.
Leon SA, Shapiro B, Sklaroff DM, Yaros MJ. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 1977; 37: 646-650.
Spindler KL, Sorensen MM, Pallisgaard N, Andersen RF, Havelund BM, Ploen J, et al. Phase II trial of temsirolimus alone and in combination with irinotecan for KRAS mutant metastatic colorectal cancer: outcome and results of KRAS mutational analysis in plasma. Acta Oncol 2013; 52: 963-970.
Spindler KL, Pallisgaard N, Vogelius I, Jakobsen A. Quantitative cell-free DNA, KRAS, and BRAF mutations in plasma from patients with metastatic colorectal cancer during treatment with cetuximab and irinotecan. Clin Cancer Res 2012; 18:1177-1185.
Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med 2008; 14: 985-990.
Brenner H. Colorectal cancer. Lancet 2014; 383: 1490-1502.
Gorgannezhad L, Umer M, Islam MN, Nguyen NT, Shiddiky MJA. Circulating tumor DNA and liquid biopsy: opportunities, challenges, and recent advances in detection technologies. Lab Chip 2018; 18: 1174-1196.
Pinzani P, Salvianti F, Zaccara S, Massi D, De Giorgi V, Pazzagli M, et al. Circulating cell-free DNA in plasma of melanoma patients: qualitative and quantitative considerations. Clin Chim Acta 2011; 412: 2141-2145.
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: 3966-3968.
Chen K, Zhang H, Zhang LN, Ju SQ, Qi J, Huang DF, et al. Value of circulating cell-free DNA in diagnosis of hepatocelluar carcinoma. World J Gastroenterol 2013; 19: 3143-3149.
Frattini M, Gallino G, Signoroni S, Balestra D, Battaglia L, Sozzi G, et al. Quantitative analysis of plasma DNA in colorectal cancer patients: a novel prognostic tool. Ann N Y Acad Sci 2006; 1075: 185-190.
Laufer-Geva S, Rozenblum AB, Twito T, Grinberg R, Dvir A, Soussan-Gutman L, et al. The Clinical Impact of Comprehensive Genomic Testing of Circulating Cell-Free DNA in Advanced Lung Cancer. J Thorac Oncol 2018; 13: 1705-1716.
Zhou S, Xu B, Qi L, Zhu D, Liu B, Wei J. Next-generation sequencing reveals mutational accordance between cell-free DNA from plasma, malignant pleural effusion and ascites and directs targeted therapy in a gastric cancer patient. Cancer Biol Ther 2018; 20: 15-20.
Hsieh CC, Hsu HS, Chang SC, Chen YJ. Circulating Cell-Free DNA Levels Could Predict Oncological Outcomes of Patients Undergoing Esophagectomy for Esophageal Squamous Cell Carcinoma. Int J Mol Sci 2016; 17: 12.
Kamel AM, Teama S, Fawzy A, EI Deftar M. Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer. Tumour Biol 2016; 37: 7565-7572.
Huang A, Zhang X, Zhou SL, Cao Y, Huang XW, Fan J, et al. Plasma Circulating Cell-free DNA Integrity as a Promising Biomarker for Diagnosis and Surveillance in Patients with Hepatocellular Carcinoma. J Cancer 2016; 7: 1798-1803.
Yoruker EE, í–zgür E, Keskin M, Dalay N, Holdenrieder S, Gezer U. Assessment of circulating serum DNA integrity in colorectal cancer patients. Anticancer Res 2015; 35: 2435-2440.
Cheng J, Cuk K, Heil J, Golatta M, Schott S, Sohn C, et al. Cell-free circulating DNA integrity is an independent predictor of impending breast cancer recurrence. Oncotarget 2017; 8: 54537-54547.
Aarthy R, Mani S, Velusami S, Sundarsingh S, Rajkumar T. Role of Circulating Cell-Free DNA in Cancers. Mol Diagn Ther 2015; 19: 339-350.
Yang J, Cheng L, Zhang J, Chen L, Wang D, Guo X, et al. Predictive value of circulating cell-free DNA in the survival of breast cancer patients: A systemic review and meta-analysis. Med (Baltimore) 2018; 97: 11417.