Pathology & Oncology Research

, Volume 25, Issue 2, pp 567–575 | Cite as

Hypermethylated Promoters of Secreted Frizzled-Related Protein Genes are Associated with Colorectal Cancer

  • Haochang Hu
  • Tiangong Wang
  • Ranran Pan
  • Yong Yang
  • Bin Li
  • Cong Zhou
  • Jun Zhao
  • Yi HuangEmail author
  • Shiwei DuanEmail author
Original Article


Colorectal cancer (CRC) is one of the leading causes of death worldwide. Aberrant DNA methylation has been recognized as one of the most common molecular alterations in CRC. The goal of this study was to investigate the diagnostic value of SFRP1 and SFRP2 methylation for CRC. A total of 80 pairs of CRC patients were recruited to test the association of SFRP1 and SFRP2 promotor methylation with CRC. Methylation assay was performed using quantitative methylation-specific polymerase chain reaction (qMSP) method. In this study, we found the methylation levels of SFRP1 and SFRP2 in CRC tumor tissues were significantly higher than those in the adjacent non-tumor tissues (SFRP1: P = 2E-5; SFRP2: P = 0.014). Further bioinformatics analysis of TCGA data confirmed the association of the two genes with CRC (SFRP1: P = 7E-21; SFRP2: P = 5E-24). Luciferase reporter gene assay showed that the recombinant plasmids with SFRP1 and SFRP2 fragments could significantly enhance promoter activity (SFRP1: P = 0.002; SFRP2: P = 0.004). In addition, SFRP1 and SFRP2 methylation were inversely correlated with the mRNA expression displayed by TCGA data mining (SFRP1: r = −0.432, P = 4E-11; SFRP2: r = −0.478, P = 1E-13). GEO data analysis indicated that SFRP1 and SFRP2 expression were increased in three CRC cell lines (COLO320, HCT116 and HT29) after 5′-AZA-deoxycytidine treatment, suggesting that DNA methylation played an important role in regulating gene expression of the two genes. Our results confirmed that promoter methylation of SFRP1 and SFRP2 contributed to the risk of CRC.


SFRP1 SFRP2 DNA methylation Colorectal cancer Quantitative methylation specific PCR 



The research is supported by grants from K. C. Wong Magna Fund in Ningbo University.

Author’s Contribution

SD and HH contribute to the conception, design and final approval of the submitted version. TW, CZ, RP and HH contribute to interpretation of data and completion of figures and Tables. YY, BL and JZ contribute to performing the experiments and analyzing the data. HH, TW and SD contribute to writing the paper. All the authors have read and approved the final manuscript.

Compliance with Ethical Standards

Conflicts of Interest

The authors declare no conflicts of interest.


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Copyright information

© Arányi Lajos Foundation 2018

Authors and Affiliations

  1. 1.Medical Genetics Center, School of MedicineNingbo UniversityNingboChina
  2. 2.Department of Neurosurgery of Ningbo First HospitalNingbo University School of MedicineNingboChina

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