Abstract 4783: Expression of genes panel related to WNT- signaling in colorectal cancer Human Papillomavirus-positive colorectal cancer.
Authors: Bernabe-Dones Raul D. , Fonseca-Williams Sharon C. , Lacourt-Ventura Mercedes Y. , Muñoz Cristina , Tirado-Gomez Maribel , Cruz-Correa Marcia R. 
Published: August 2014

The Wnt signaling pathway is conserved in various species and plays significant roles in development, cellular proliferation and differentiation. WNT signaling comprises three pathways: the canonical pathway and two non-canonical pathways. Moreover, it is generally accepted that both dysfunction of the Wnt signaling pathway, including mutations in the adenomatous polyposis coli (APC) and b-catenin genes, and genetic instability play important roles in colorectal carcinogenesis. However, alterations of the components of the Wnt signaling pathways in CRC have not been totally elucidated. Several studies support a possible role of Human Papillomavirus in colorectal carcinogenesis. The aim of this study was to comprehensively investigate the expression profiles of Wnt signaling components in HPV-positive and HPV-negative CRC cases using real-time PCR analysis.

Methods: To determine the expression profile of the association of HPV and CRC, we conducted an age-matched case study in four HPV-positive and four HPV-negative CRC cases. We employed the Human WNT Signaling Pathway RT² Profiler PCR Array (Qiagen) to assay the expression of 84 genes related to WNT-mediated signal transduction. This array contains WNT signaling ligands and receptors as well as other downstream signaling molecules for all three WNT pathways. Results were evaluated with the RT² PCR Data Analysis Software provided by Qiagen.

Results: Four male HPV-positive CRC cases (mean ages was 56 ± 2 years) and four HPV-negative CRC cases (mean ages 57 ± 2 years) were analyzed using the RT² Profiler™ PCR Array Human WNT Signaling Pathway (Qiagen). We detected a decrease in the expression levels of three WNT-canonical signaling molecules in HPV-positive CRC cases when compared to HPV-negative cases. The BCL9, LRP5 and WNT3 showed a 39% (p = 0.049), 43% (p = 0.020) and 60% (p=0.038) decrease in expression in HPV-positive cases, respectively. Reduced expression of three WNT signaling negative regulator genes was also observed: CTMP1 decreased 49% (p= 0.006), CXX4 decreased 49% (p=0.029) and FBXW11 expression decreased 41% (p = 0.041).

Conclusion: Our findings suggest that colorectal tumors infected with HPV could define a non-described subtype of CRC based in the expression of a focused panel of genes related to WNT-mediated signal transduction. These results suggest an alteration of the WNT canonical pathway as a consequence of HPV infection in CRC.

Citation Format: Raul D. Bernabe-Dones, Sharon C. Fonseca-Williams, Mercedes Y. Lacourt-Ventura, Cristina Muñoz, Maribel Tirado-Gomez, Marcia R. Cruz-Correa. Expression of genes panel related to WNT- signaling in colorectal cancer Human Papillomavirus-positive colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4783. doi:10.1158/1538-7445.AM2013-4783