Long‑fragment DNA as a potential marker for stool‑based detection of colorectal cancer

Zhang,Yibo; Suehiro,Yutaka; Shindo,Yoshitaro; Sakai,Kouhei; Hazama,Shoichi; Higaki,Shingo; Sakaida,Isao; Oka,Masaaki; Yamasaki,Takahiro

doi:10.3892/ol.2014.2632

Long‑fragment DNA as a potential marker for stool‑based detection of colorectal cancer

Authors:
- Yibo Zhang
- Yutaka Suehiro
- Yoshitaro Shindo
- Kouhei Sakai
- Shoichi Hazama
- Shingo Higaki
- Isao Sakaida
- Masaaki Oka
- Takahiro Yamasaki
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Affiliations: Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan, Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan, Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan
Published online on: October 24, 2014 https://doi.org/10.3892/ol.2014.2632
Pages: 454-458

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Abstract

Neoplastic cells that are exfoliated from the colorectal epithelium exhibit dysfunctional apoptotic mechanisms, and thus it is possible to identify high‑molecular‑weight DNA fragments (long DNA) in feces. In the present study, the sensitivity and specificity of fecal‑based long DNA assays were evaluated for the detection of colorectal cancer (CRC). Feces were collected from 54 healthy volunteers and 130 patients with CRC prior to surgical treatment. The presence of long DNA of the adenomatosis polyposis coli, Kirsten rat sarcoma viral oncogene homolog (KRAS), B‑raf proto‑oncogene, serine/threonine kinase and p53 genes was assessed by polymerase chain reaction followed by electrophoresis. The identification of long DNA in feces was found to exhibit a sensitivity of 56.2% and specificity of 96.3% for CRC detection. In addition, long DNA was identified in the feces of 58/90 (64.4%) patients with distal CRC and 15/40 (37.5%) patients with proximal CRC. This study indicates the potential of the fecal long DNA assay as a non‑invasive and easily performed method for the detection of individuals with CRC.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Pawa N, Arulampalam T and Norton JD: Screening for colorectal cancer: established and emerging modalities. Nat Rev Gastroenterol Hepatol. 8:711–722. 2011. View Article : Google Scholar : PubMed/NCBI
3	Di Lena M, Travaglio E and Altomare DF: New strategies for colorectal cancer screening. World J Gastroenterol. 19:1855–1860. 2013. View Article : Google Scholar : PubMed/NCBI
4	Ahlquist DA and Shuber AP: Stool screening for colorectal cancer: evolution from occult blood to molecular markers. Clin Chim Acta. 315:157–168. 2002. View Article : Google Scholar
5	van Turenhout ST, Oort FA, Terhaar sive Droste JS, et al: Hemorrhoids detected at colonoscopy: an infrequent cause of false-positive fecal immunochemical test results. Gastrointest Endosc. 76:136–143. 2012. View Article : Google Scholar : PubMed/NCBI
6	van Rossum LG, van Rijn AF, Laheij RJ, et al: Random comparison of guaiac and immunochemical fecal occult blood tests for colorectal cancer in a screening population. Gastroenterology. 135:82–90. 2008. View Article : Google Scholar : PubMed/NCBI
7	Velez JP, Schwesinger WH, Stauffer J, et al: Bidirectional endoscopy in patients with fecal occult blood. Surg Endosc. 16:117–120. 2002. View Article : Google Scholar : PubMed/NCBI
8	Luo X, Stock C, Burwinkel B and Brenner H: Identification and evaluation of plasma microRNAs for early detection of colorectal cancer. PLoS One. 8:e628802013. View Article : Google Scholar : PubMed/NCBI
9	Carmona FJ, Azuara D, Berenguer-Llergo A, et al: DNA methylation biomarkers for noninvasive diagnosis of colorectal cancer. Cancer Prev Res (Phila). 6:656–665. 2013. View Article : Google Scholar
10	Calistri D, Rengucci C, Bocchini R, et al: Fecal multiple molecular tests to detect colorectal cancer in stool. Clin Gastroenterol Hepatol. 1:377–383. 2003. View Article : Google Scholar
11	Leung WK, To KF, Man EP, et al: Detection of epigenetic changes in fecal DNA as a molecular screening test for colorectal cancer: a feasibility study. Clin Chem. 50:2179–2182. 2004. View Article : Google Scholar : PubMed/NCBI
12	Dong SM, Traverso G, Johnson C, et al: Detecting colorectal cancer in stool with the use of multiple genetic targets. J Natl Cancer Inst. 93:858–865. 2001. View Article : Google Scholar : PubMed/NCBI
13	Leung WK, To KF, Man EP, et al: Detection of hypermethylated DNA or cyclooxygenase-2 messenger RNA in fecal samples of patients with colorectal cancer or polyps. Am J Gastroenterol. 102:1070–1076. 2007. View Article : Google Scholar : PubMed/NCBI
14	Kalimutho M, Del Vecchio Blanco G, Cretella M, et al: A simplified, non-invasive fecal-based DNA integrity assay and iFOBT for colorectal cancer detection. Int J Colorectal Dis. 26:583–592. 2011. View Article : Google Scholar : PubMed/NCBI
15	Loganayagam A: Faecal screening of colorectal cancer. Int J Clin Pract. 62:454–459. 2008. View Article : Google Scholar
16	Ahlquist DA: Molecular detection of colorectal neoplasia. Gastroenterology. 138:2127–2139. 2010. View Article : Google Scholar : PubMed/NCBI
17	Boynton KA, Summerhayes IC, Ahlquist DA and Shuber AP: DNA integrity as a potential marker for stool-based detection of colorectal cancer. Clin Chem. 49:1058–1065. 2003. View Article : Google Scholar : PubMed/NCBI
18	Kalimutho M, del Blanco GV, Gravina P, et al: Quantitative denaturing high performance liquid chromatography (Q-dHPLC) detection of APC long DNA in faeces from patients with colorectal cancer. Clin Chem Lab Med. 48:1303–1311. 2010. View Article : Google Scholar : PubMed/NCBI
19	Calistri D, Rengucci C, Molinari C, et al: Quantitative fluorescence determination of long-fragment DNA in stool as a marker for the early detection of colorectal cancer. Cell Oncol. 31:11–17. 2009.
20	Bedi A, Pasricha PJ, Akhtar AJ, et al: Inhibition of apoptosis during development of colorectal cancer. Cancer Res. 55:1811–1816. 1995.PubMed/NCBI
21	Arends MJ, Morris RG and Wyllie AH: Apoptosis. The role of the endonuclease. Am J Pathol. 136:593–608. 1990.PubMed/NCBI
22	Japanese Society for Cancer of the Colon and Rectum. Japanese Classification of Colorectal Carcinoma. 8th edition. Kanehara & Co., Ltd; Tokyo: pp. 172013
23	Tsujitani S, Shirai H, Tatebe S, et al: Apoptotic cell death and its relationship to carcinogenesis in colorectal carcinoma. Cancer. 77(Suppl 8): 1711–1716. 1996. View Article : Google Scholar : PubMed/NCBI
24	Ahlquist DA, Harrington JJ, Burgart LJ and Roche PC: Morphometric analysis of the “mucocellular layer” overlying colorectal cancer and normal mucosa: relevance to exfoliation and stool screening. Human Pathol. 31:51–57. 2000. View Article : Google Scholar
25	Sträter J, Wedding U, Barth TF, Koretz K, Elsing C and Möller P: Rapid onset of apoptosis in vitro follows disruption of beta 1-integrin/matrix interactions in human colonic crypt cells. Gastroenterology. 110:1776–1784. 1996. View Article : Google Scholar : PubMed/NCBI
26	Peitsch MC, Mannherz HG and Tschopp J: The apoptosis endonucleases: cleaning up after cell death? Trends Cell Biol. 4:37–41. 1994. View Article : Google Scholar : PubMed/NCBI
27	Caldarella A, Crocetti E, Messerini L and Paci E: Trends in colorectal incidence by anatomic subsite from 1985 to 2005: a population-based study. Int J Colorectal Dis. 28:637–641. 2013. View Article : Google Scholar : PubMed/NCBI
28	Zou H, Harrington JJ, Klatt KK and Ahlquist DA: A sensitive method to quantify human long DNA in stool: relevance to colorectal cancer screening. Cancer Epidemiol Biomarkers Prev. 15:1115–1119. 2006. View Article : Google Scholar : PubMed/NCBI