Serum cell-free DNA concentrations and integrity analysis of colorectal cancer patients before and after surgery

Guangxin Cao; Yu Xie; Xiaohui Jiang; Xiaofeng Tian; Ding Wang; Yan Sun

doi:10.14715/cmb/2019.65.6.8

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Vol. 65 No. 6: Issue 6

Issue Published : August 5, 2019

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Serum cell-free DNA concentrations and integrity analysis of colorectal cancer patients before and after surgery

https://doi.org/10.14715/cmb/2019.65.6.8

Guangxin Cao

Department of General Surgery, Nantong Tumor Hospital. No.48, West Youth Road, 226361 Nantong, Jiangsu province, China

Yu Xie

Department of Geratology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008 Nanjing, Jiangsu Province, China

Xiaohui Jiang

Department of General Surgery, Nantong Tumor Hospital. No.48, West Youth Road, 226361 Nantong, Jiangsu province, China

Xiaofeng Tian

Endoscopy Center, Nantong Tumor Hospital. No.48, West Youth Road, 226361 Nantong, Jiangsu province, China

Ding Wang

Department of General Surgery, Nantong Tumor Hospital. No.48, West Youth Road, 226361 Nantong, Jiangsu province, China

Yan Sun

Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, 210009 Nanjing, Jiangsu Province, China

Corresponding Author(s) : Yan Sun

sunyan@188.com

Cellular and Molecular Biology, Vol. 65 No. 6: Issue 6
Article Published : July 31, 2019

Abstract

This study was carried out to investigate cell-free DNA (cfDNA) as a potential biomarker for colorectal cancer diagnosis.Patients with colorectal cancer (n = 25) who had not undergone surgery, and 35 patients with postoperative colorectal cancer were enrolled. Peripheral blood samples were collected from the colorectal cancer subjects (experimental group), and also from 30 healthy volunteers (control group). Quantitative PCR (qPCR) was used to determine cfDNA concentration and integrity in each group. The cfDNA levels of the two groups were analyzed to determine the relationship between the cfDNA and the clinical features of colorectal cancer patients. The receiver operator curve (ROC) was used to analyze sensitivity and specificity of cfDNA, carcinoembryonic antigen (CEA), cancer antigen 199 (CA199) and cancer antigen 125 (CA125). cfDNA concentration and cfDNA integrity 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 of the healthy control group, but the integrity was not significantly different from the control group. There was no significant correlation between cfDNA concentration/integrity and gender, age, disease stage, tumor location, tumor differentiation, and expressions of cancer antigen 153 (CA153), neuron specific enolase (NSE) and alpha fetoprotein (AFP) in colorectal cancer patients before or after surgery. However, there was a significant correlation between the expression levels of CEA/CA125 and concentration of cfDNA. The CA199 expression level was significantly correlated with cfDNA integrity. The sensitivity and specificity of cfDNA and integrity were higher than those used for traditional tumor biomarker detection. cfDNA concentration is significantly increased in serum of colorectal cancer patients. Thus, it may serve as a potential indicator of colorectal cancer.

Keywords

Cell-free DNA Colorectal cancer CA199 CA125 CEA ROC curve.

Cao, G., Xie, Y., Jiang, X., Tian, X., Wang, D., & Sun, Y. (2019). Serum cell-free DNA concentrations and integrity analysis of colorectal cancer patients before and after surgery. Cellular and Molecular Biology, 65(6), 44–51. https://doi.org/10.14715/cmb/2019.65.6.8

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References

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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.
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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.
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.
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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.

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.

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.

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.

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.

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.

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.

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.

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.

Author biographies is not available.