Downregulation of WIF-1 and Wnt5a in patients with colorectal carcinoma: clinical significance - PubMed (original) (raw)

. 2014 Aug;35(8):7975-82.

doi: 10.1007/s13277-014-2015-9. Epub 2014 May 16.

Affiliations

Free article

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

Rania Abdelmaksoud-Dammak et al. Tumour Biol. 2014 Aug.

Free 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.

PubMed Disclaimer

References

    1. Nucleic Acids Res. 2002 May 1;30(9):e36 - PubMed
    1. Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9821-6 - PubMed
    1. Cancer Res. 2005 Oct 15;65(20):9142-6 - PubMed
    1. PLoS One. 2013 Nov 18;8(11):e80526 - PubMed
    1. Cancer Metastasis Rev. 2004 Jan-Jun;23(1-2):29-39 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources