Coexpression of SFRP1 and WIF1 as a prognostic predictor of favorable outcomes in patients with colorectal carcinoma.

Shiyong Huang,Chun Yang,Zikang Li,Hongyu Wu,Long Cui,Peng Du,Shijie Yang,Jun Gao,Shuming Zi,Rongfeng Song,Xiaoming Zhong

doi:10.1155/2014/256723

Abstract

Colorectal tumorigenesis is ascribed to the activity of Wnt signaling pathway in a ligand-independent manner mainly through APC and CTNNB1 gene mutations and in a ligand-dependent manner through low expression of Wnt inhibitors such as WNT inhibitory factor 1 (WIF1) and secreted frizzled related protein 1 (SFRP1). In this study we found that WIF1 protein expression was increased and SFRP1 was decreased significantly in CRC tissue versus normal tissue, and high expression of WIF1 was associated with big tumor diameters and deep invasion, and loss of SFRP1 expression was associated with the left lesion site, deep invasion, and high TNM stage. Among the four expression patterns (WIF+/SFRP1+, WIF+/SFRP1−, WIF−/SFRP1+, and WIF−/SFRP1−) only coexpression of WIF1 and SFRP1 (WIF+/SFRP1+) was associated with favorable overall survival, together with low TNM stage, as an independent prognostic factor as shown in a multivariate survival model. The results indicated that WIF1 seemed to play an oncogenic role, while SFRP1 seemed to play an oncosuppressive role although both of them are secreted Wnt antagonists. Coexpression of SFRP1 and WIF1, rather than SFRP1 or WIF1 alone, could be used, together with low TNM stage, as a prognostic predictor of favorable outcomes in CRC.

Highlights

Colorectal cancer (CRC) is a common malignant tumor worldwide, and the incidence of which has increased rapidly over the past decade
In this study we found that WNT inhibitory factor 1 (WIF1) protein expression was increased and secreted frizzled related protein 1 (SFRP1) was decreased significantly in CRC tissue versus normal tissue, and high expression of WIF1 was associated with big tumor diameters and deep invasion, and loss of SFRP1 expression was associated with the left lesion site, deep invasion, and high TNM stage
The present study provided the first evidence that SFRP1 and WIF1 were differentially expressed in CRC, and their coexpression, rather than SFRP1 or WIF1 alone, was associated with a favorable prognosis

Summary

Introduction

Colorectal cancer (CRC) is a common malignant tumor worldwide, and the incidence of which has increased rapidly over the past decade. The transduction of Wnt signals between cells proceeds via a complex series of events, including posttranslational modification and secretion of Wnts, binding to transmembrane receptors, activation of cytoplasmic effectors, and transcriptional regulation of target genes [3, 4]. Aberrant regulation of the Wnt signalling pathway has been suggested to play a role in tumorigenesis [5, 6], especially in the pathogenesis of CRC [7]. Increasing evidence suggests that dysregulation of Wnt signaling by secreted antagonists on the cell surface is associated with tumorigenesis [10,11,12,13,14,15]; for example, the low expression induced by promoter methylation of BioMed Research International

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Results

Conclusion