MicroRNAs as Diagnostic Markers for Pancreatic Ductal Adenocarcinoma and Pancreatic Intraepithelial Neoplasm
Yue Xue, Ahmad N Abou Tayoun, Kristine M Abo, J Marc Pipas, Stuart R Gordon, Timothy B Gardner, Richard J Barth, Arief A Suriawinata, Gregory J Tsongalis. Dartmouth-Hitchcock Medical Center, Lebanon, NH
Background: Since the discovery of small non-coding RNAs, the analysis of microRNA (miRNA) expression patterns in human cancer have provided new insights into cancer biology. Evidence suggests that deregulated miRNA expression is associated with pancreatic cancer development. In this study, we analyzed the expression of several miRNAs in different types of pancreatic disease to determine if miRNAs expression could aid the diagnosis of pancreatic ductal adenocarcinoma (PDAC) and its precursor – pancreatic intraepithelial neoplasm (PanIN).
Design: Resection specimens containing PDAC (n=16), paired pancreatic tissue with negative margin in each case (n=16), chronic pancreatitis (n= 4), normal pancreatic parenchyma (n=5), PanIN (n=5) with different grade of dysplasia (I to III) were selected from our department archive between 2004 and 2011. These formalin-fixed paraffin embedded tissue blocks were evaluated for miR-148a, miR-196 and miR-217 expression by quantitative reverse transcription polymerase chain reaction.
Results: Our data show that miR-148a and miR-217 expression levels were significantly down-regulated in PanIN and PDAC compared to the normal pancreatic parenchyma. Comparison of these miRNA levels between the neoplastic lesions and chronic pancreatitis showed that miR-148a (P < 0.05) and miR-217 levels (P < 0.0001) were much lower in PDAC. Dramatic reduction of expression levels in PDAC was further confirmed by comparing their levels in PDAC and paired controls with negative margin which predominantly consists of chronic pancreatitis. In addition, we observed that miR-148a levels were much lower in PanIN than in chronic pancreatitis (P < 0.05). MiR-217 expression level also decreased, although to a lesser extent, in PanIN compared to in chronic pancreatitis (P = 0.09). In contrast, the level of miR-196 expression was significantly overexpressed in PanIN (P<0.0001) and PDAC (P<0.0001) compared to the non-neoplastic pancreatic parenchyma. Interestingly, the degree of deregulation of all three miRNA markers is much higher in PanIN II-III compared to that in PanIN I.
Conclusions: Our study demonstrates that miR-148a, miR-217 and miR-196a are significantly deregulated in pancreatic ductal adenocarcinoma, including in the early stage of the pancreatic ductal adenocarcinoma. Thus, these markers can be potentially used as diagnostic markers to distinguish pancreatic ductal adenocarcinoma and its precursor from benign lesions.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 167, Tuesday Afternoon