Abstract 4680: Correlation between Wnt pathway and colorectal cancer recurrence using protein, mRNA and microRNA analysis

Abstract

Abstract BACKGROUND: Wnt signaling pathway has a fundamental role in colorectal carcinogenesis. However, few studies have focused in the association of this pathway and the risk of postoperative recurrence. Besides microRNAs repress protein translation through binding to targets mRNAs and have shown association with specific targets. The main goal of this study was to evaluate several members of Wnt signaling pathway (Wnt protein family, proteins from β-catenin/APC complex, transcription factors and target proteins) and CRC recurrence. We also would like to assess association of microRNAs with specific Wnt targets or the direct implication of those small non coding RNAs with CRC recurrence. METHODS: The expression of Wnt proteins and mRNAs were assessed using immunohistochemistry and Real Time-PCR techniques, respectively. We also studied 381 microRNAs using Low Density TaqMan Array. This study was performed in samples from patients presenting stages I and II CRC and comparing those who had recurrence to those who did not. All patients undergone surgery with curative intention from 2000 to 2006 in A. C. Camargo Hospital. Statistical analyses used in this study were Chi-square, exact Fisher's test and T Paired. RESULTS: Regarding the protein expression and gene expression of Wnt signaling members only c-Myc showed statistically significant association with recurrence (p=0,001 and p=0,048, respectively). Regarding the analysis of 381 microRNAs, a statistically significant association was observed for miR-197 (p=0,03), where the group of patients who did not had recurrence demonstrated higher expression levels of this microRNA when compared to the group of patients who developed tumor recurrence. CONLUSION: Increased levels of c-Myc expression and low levels of miR-197 in the tumor may be used at the time of primary removal for defining patients at risk for tumor recurrence. miR-197 may regulate indirectly the expression of c-Myc. However, further experiments will be required to better evaluate this hypothesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4680.