|
|
Back to Annual Meeting Program
LRP6 Overexpression As a Potential Marker of Early Stage Tumor Progression in Pancreatic Ductal Adenocarcinoma
Nicolas Zea1,3, William C. Conway1, John S. Bolton1, Nancy K. Davis6, Cruz Velasco5, Paul B. Fossier4, Jovanny Zabaleta*2,3
1General Surgery, Ochsner Clinic Foundation, New Orleans, LA; 2Pediatrics, LSU Health Sciences Center, New Orleans, LA; 3Stanley S. Scott Cancer Center, LSU Health Sciences Center, New Orleans, LA; 4School of Medicine, LSU Health Sciences Center, New Orleans, LA; 5School of Public Health, LSU Health Sciences Center, New Orleans, LA; 6Anatomic Pathology, Ochsner Clinic Foundation, New Orleans, LA
Introduction: The Wnt-β-Catenin signaling pathway, in particular the canonical pathway, has been implicated in pancreatic ductal adenocarcinoma (PDAC) development. Since mutations in the key intracellular components of this pathway are rare in PDAC, understanding the molecular mechanisms by which the signaling pathway is aberrantly activated, and how it influences tumor behavior, is of utmost importance. In this study, we hypothesized that over-expression of components upstream of the signaling pathway, in particular the Wnt signaling co-receptor LRP6, are involved in PDAC tumorigenesis.
Methods: Twelve lymph node negative (LN-) and twelve lymph node positive (LN+) paraffin embedded tumor tissues were randomly selected to perform screening gene identification via gene chip microarray analysis. Once genes of interest were identified by fold-change, 61 tumor samples were obtained and then subcategorized in terms of lymph node status, survival time, and grade of differentiation and used to validate the results using real-time PCR (RT-PCR).
Results: 20,817 genes were investigated with the microarray analysis. Using gene chip microarray software, we removed the background and used scatter graphs to select those genes with at least 2-fold difference (up or down) between LN- and LN+. Further selection by p value (p<0.05) identified 957 genes significantly different between the two groups. The LRP6 gene expression showed a 2.46-fold increase in the LN- when compared to LN+ samples (1192.9 vs 485). RT-PCR for LRP6 in LN- (n=29) and LN+ (n=32) confirmed results of the microarray (p-value=0.00044). In addition, LRP6 showed a trend of over-expression towards tumors of lower grades of differentiation (table 1). In terms of survival time, no statistical significance was found between LN- and LN+.
Conclusions: The Wnt signaling co-receptor LRP6 is one of the most upstream genes involved in the Wnt-β-Catenin signaling pathway. Our data shows that LRP6 is significantly over-expressed in patients with negative nodal status, as well as portraying a tendency of over-expression in lower differentiation grades of pancreatic tumor. Our results reflect an over-expression of LRP6 early in the series of tumorigenesis events and depict the importance of further studies to understand its relationship to tumor behavior and prognosis.
Difference within tumor samples regarding grade of differentiation
| Gene | N Samples | Grade | Average Fold Induction | | LRP6 | 6 | na | 2.24 | | 1 | undifferentiated | 2.28 | | 15 | poor | 2.08 | | 27 | moderate | 2.45 | | 12 | well | 3.41 |
Back to Annual Meeting Program
|
