Tumor Biology

, Volume 35, Issue 10, pp 10457–10465 | Cite as

Variation risks of SFRP2 hypermethylation between precancerous disease and colorectal cancer

  • Chengguang Sui
  • Guang Wang
  • Qun Chen
  • Jianzhong MaEmail author
Research Article


DNA hypermethylation of secreted frizzled-related protein 2 (SFRP2) gene associated with the Wnt signaling pathway has been studied previously. However, the risk size and changing rules between colorectal cancer (CRC) and SFRP2 hypermethylation from precancerous disease to CRC remain unclear. The aim of work was therefore to investigate the risk size and changing rule based on detections on large numbers of tissue and feces samples. Association study and meta-analysis were performed to analyze the risk size of SFRP2 hypermethylation in tissue and fecal detections from 2,912 samples, including 1,436 patients with CRC, 866 patients with colon adenomas or polyps, and 610 samples with both normal controls. Based on normal controls as standard reference, the analysis showed that SFRP2 hypermethylation in CRC and adenoma tissues had a significantly higher risk with 92.81 (28.76–299.45) and 22.46 (4.13–122.04) odds ratio (OR) (95 % confidence interval (CI)) respectively, and that the risk sizes of SFRP2 hypermethylation in CRC and adenoma patients were 41.86 (18.91–92.67) and 11.76 (6.98–19.84) of OR (95 % CI) in fecal samples, and that the OR risk in both tissue and fecal samples increased significantly to 70.35 and 30.10 from precancerous disease (adenoma or polyp) to CRC. There were significant differences between tissue and fecal hypermethylation frequency. On the basis of the hypermethylation frequency of colorectal tissue, the coincidence rates of fecal hypermethylation in CRC and colorectal adenoma were 0.89 and 0.9, respectively. The risk size of SFRP2 hypermethylation from normal control to adenoma or polyp as well as from adenoma or polyp to CRC increased gradually in both tissue and feces. Therefore, SFRP2 hypermethylation is an important biomarker both in noninvasive diagnosis in feces detection and in colon tissue.


Colorectal tumor Hypermethylation SFRP2 gene Variation rule 


Conflicts of interest



  1. 1.
    Ahn JB, Chung WB, Maeda O, Shin SJ, Kim HS, et al. DNA methylation predicts recurrence from resected stage III proximal colon cancer. Cancer. 2011;117:1847–54.PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Kawano Y, Kypta R. Secreted antagonists of the Wnt signaling pathway. J Cell Sci. 2003;116:2627–34.CrossRefPubMedGoogle Scholar
  3. 3.
    Kondo Y, Issa JP. Epigenetie changes in colorectal cancer. Cancer Metast Rev. 2004;23(1–2):29–39.CrossRefGoogle Scholar
  4. 4.
    Dhir M, Montgomery EA, Glöckner SC, Schuebel KE, Hooker CM, Herman JG, et al. Epigenetic regulation of WNT signaling pathway genes in inflammatory bowel disease (IBD) associated neoplasia. Gastrointest Surg. 2008;12(10):1745–53.CrossRefGoogle Scholar
  5. 5.
    Chen WD, Han ZJ, Skoletsky J, et al. Detection in fecal DNA of colon cancer-specific methylation of the nonexpressed vimentin gene. J Natl Cancer Inst. 2005;97(15):1124–32.CrossRefPubMedGoogle Scholar
  6. 6.
    Camp ER, Findlay VJ, Vaena SG, Walsh J, Lewin DN, Turner DP, et al. Slug expression enhances tumor formation in a noninvasive rectal cancer model. J Surg Res. 2011;170(1):56–63.PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Nagasaka T, Tanaka N, Cullings HM, Sun DS, Sasamoto H, Uchida T, et al. Analysis of fecal DNA methylation to detect gastrointestinal neoplasia. J Natl Cancer Inst. 2009;101(18):1244–58.PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Takeda M, Nagasaka T, Dong-Sheng S, Nishie H, Oka T, Yamada E, et al. Expansion of CpG methylation in the SFRP2 promoter region during colorectal tumorigenesis. Acta Med Okayama. 2011;65(3):169–77.PubMedGoogle Scholar
  9. 9.
    Pehlivan S, Artac M, Sever T, Bozcuk H, Kilincarslan C, Pehlivan M. Gene methylation of SFRP2, P16, DAPK1, HIC1, and MGMT and KRAS mutations in sporadic colorectal cancer. Cancer Genet Cytogenet. 2010;201:128–32.CrossRefPubMedGoogle Scholar
  10. 10.
    Müller HM, Oberwalder M, Fiegl H, Morandell M, Goebel G, Zitt M, et al. Methylation changes in fecal DNA: a marker for colorectal cancer screening? Lancet. 2004;363(9417):1283–85.CrossRefPubMedGoogle Scholar
  11. 11.
    Oberwalder M, Zitt M, Wöntner C, Fiegl H, Goebel G, Zitt M, et al. SFRP2 methylation in fecal DNA—a marker for colorectal polyps. Int J Colorectal Dis. 2008;23:15–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Chang E, Park DI, Kim YJ, Kim BK, Park JH, Kim HJ, et al. Detection of colorectal neoplasm using promoter methylation of ITGA4, SFRP2, and p16 in stool samples: a preliminary report in Korean patients. Hepatogastroenterology. 2010;57(101):720–27.PubMedGoogle Scholar
  13. 13.
    Dao-rong W, Dong T. A study on relation of hypermethylation of secreted frizzled-related protein 2 (SFRP2) gene with colorectal cancer. Acta Univ Med Nanjing. 2007;27(11):1240–43.Google Scholar
  14. 14.
    QI Jian, Zhu You-qing, LI Xia, et a1. Hypermethylation and expression of secreted frizzled-related proteins genes in different stages of colorectal tumor. Chin J Dig. 2007; 27 (4):251–54Google Scholar
  15. 15.
    Huang Z-H. Detection of aberrant methylation in fecal DNA as a molecular screening tool for colorectal cancer and precancerous lesions. World J Gastroenterol. 2007;13(6):950–54.PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Tang D, Wang D-r, Li H-b. Combination analysis of hypermethyIated SFRPl and SFRP2 gene in fecal as a novel epigenetic biomarker panel for colorectal cancer screening. Journal of Nanjing Medical University. 2008;22(2):96–101.CrossRefGoogle Scholar
  17. 17.
    Tang D, Xue Y-j, Wen-jie F, Wang D-r. Study of the role of methylated SFRP2 gene in colorectal cancer screening. Chin J Curr Adv Gen Surg. 2009;12(5):378–82.Google Scholar
  18. 18.
    Tang D, Wang D-r, Hai-feng Y, Li Y-k. The expression of hypermethylated secreted frizzled-related protein 2 gene in colorectal cancer. Chin J Gen Surg. 2010;25(6):480–83.Google Scholar
  19. 19.
    Yu H-f, Wang G-r, Zhang Y, Jiang C, et al. SFRP2 gene promoter hypermethylation and its clinicopathologic significance in colorectal carcinoma. Int J Surg. 2011;39(8):526–29.Google Scholar
  20. 20.
    Wai. K Leung, Ka-Fai To, Ellen P.S. Man, Michael W.Y. Chan, et al. Detection of hypermethylated DNA or cyclooxygenase-2 messenger RNA in fecal samples of patients with colorectal cancer or polyps. Am J Gastroenteol. 2007; 102:1070–76Google Scholar
  21. 21.
    Pack SC, Kim HR, Lim SW, Kim HY, Ko JY, Lee KS, et al. Usefulness of plasma epigenetic changes of five major genes involved in the pathogenesis of colorectal cancer. Int J Colorectal Dis. 2013;28(1):139–47.CrossRefPubMedGoogle Scholar
  22. 22.
    Azuara D, Rodriguez-Moranta F, de Oca J, Sanjuan X, Guardiola J, Lobaton T, et al. Novel methylation panel for the early detection of neoplasia in high-risk ulcerative colitis and Crohn’s colitis patients. Inflamm Bowel Dis. 2013;19(1):165–73.CrossRefPubMedGoogle Scholar
  23. 23.
    Li YW, Kong FM, Zhou JP, Dong M. Aberrant promoter methylation of the vimentin gene may contribute to colorectal carcinogenesis: a meta-analysis. Tumour Biol. 2014. DOI  10.1007/s13277-014-1905-1

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Chengguang Sui
    • 1
  • Guang Wang
    • 2
  • Qun Chen
    • 3
  • Jianzhong Ma
    • 4
    Email author
  1. 1.Cancer Research Institute, First Affiliated HospitalChina Medical UniversityShenyangChina
  2. 2.Department of General Surgery, The First Affiliated HospitalChina Medical UniversityShenyangChina
  3. 3.School of SciencesNingxia Medical UniversityYinchuanChina
  4. 4.Department of Cell Biology, Key Lab of Medical Cell Biology, Ministry of EducationChina Medical UniversityShenyangChina

Personalised recommendations