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Tumor Biology

, Volume 35, Issue 8, pp 7975–7982 | Cite as

Downregulation of WIF-1 and Wnt5a in patients with colorectal carcinoma: clinical significance

  • Rania Abdelmaksoud-Dammak
  • Imen Miladi-Abdennadher
  • Amena Saadallah-Kallel
  • Abdelmajid Khabir
  • Tahia Sellami-Boudawara
  • Mounir Frikha
  • Jamel Daoud
  • Raja Mokdad-Gargouri
Research Article

Abstract

Activation of the wingless-type (Wnt) signaling pathway is common in various human cancers including colorectal cancer (CRC). Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist that can bind Wnt ligands and therefore inhibits the Wnt signaling pathway. In this study, we aimed to analyze the expression of two members of Wnt signaling (WIF-1 and Wnt5a) in Tunisian patients with sporadic CRC. WIF-1 was frequently methylated in tumor tissues (87.95 %) compared to normal mucosa (39.54 %) and correlated with distant metastasis and vascular invasion (P = 0.001 and 0.037, respectively). The unmethylated profile of the WIF-1 promoter conferred a benefit to patients in terms of overall survival (P log rank = 0.024). In addition, in the group of patients with methylated WIF-1 promoter, the overall survival rate was significantly prolonged for those with small tumor size (<5 cm) and absence of distant metastasis (P log rank = 0.007 and 0.036, respectively). Aberrant CpG methylation of the WIF-1 promoter leads to transcriptional silencing of this tumor suppressor gene in tumor tissues (P = 0.001). Furthermore, we showed that the level of Wnt5a mRNA was significantly lower in tumor compared to normal tissues (P = 0.031) and lower still in those showing more aggressive behavior (presence of lymph nodes and advanced TNM stage). Our finding supports that WIF-1 is frequently methylated and that Wnt5a acts as a tumor suppressor gene in CRC. Loss of WIF-1 and Wnt5a functions results in more aggressive behavior of the disease.

Keywords

Colorectal cancer CpG methylation Wnt signaling Wnt5a Tumor suppressor 

Notes

Acknowledgments

This work was supported by a grant of the Tunisian Ministry of High Education and Scientific Research.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Rania Abdelmaksoud-Dammak
    • 1
  • Imen Miladi-Abdennadher
    • 1
  • Amena Saadallah-Kallel
    • 1
  • Abdelmajid Khabir
    • 2
  • Tahia Sellami-Boudawara
    • 2
  • Mounir Frikha
    • 2
  • Jamel Daoud
    • 2
  • Raja Mokdad-Gargouri
    • 1
    • 3
  1. 1.Laboratory of Biomass Valorisation and Production of Eukaryotic Proteins, Center of Biotechnology of SfaxUniversity of SfaxSfaxTunisia
  2. 2.Centre Hospitalo-Universitaire Habib BourguibaSfaxTunisia
  3. 3.Centre de Biotechnologie de SfaxSfaxTunisia

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