Novel Progression-Associated Genes In Pancreatic Endocrine Neoplasms

15516 Background: Pancreatic endocrine tumors/carcinomas (PETs/PECAs) are clinically challenging. With the development of metastases there is significant drop in patient survival. Therefore, detection of progression-associated genes in tumor tissue can have profound prognostic and therapeutic implications. Methods: Five clinically-localized primary (CLP)-PETS from 5 patients (mean age 66; 3M/2F) and 6 metastatic primary (MP)-PECAs and matched liver metastases (MLMs) (N=12) from 6 other patients (mean age 59, 3M/3F) were selected. All tumors were flash frozen within 15 minutes of surgery and macrodissected to achieve 80–98% tumor enrichment. The tumor RNA samples were run on Affymetrix U133 2.0 gene chip. Data were RMA normalized. t-test was used to identify differentially expressed genes in MP-PECAs vs. CLP-PETs and MLMs Vs. MP-PECAs. Based on statistical and pathway analyses, gene function and extensive literature review ‘candidate progression genes’ were selected for validation by immunohistochemistry and real time PCR (q-PCR) using microfluidics cards (AB, Inc.,USA). To normalize q-PCR data, we used microfluidic cards to determine our original endogenous control genes specific for frozen and archival PETs/PECAs. Results: 217 transcripts were differentially expressed between MP- PECAs and CLP-PETs, using p-value <0.05 and fold-change values >1.5/>2/>4/>8 (217/94/19/1 gene respectively). Similarly, 330 transcripts were differentially expressed between MLMs and their matched MP-PECAs, using p-value <0.05 and fold-change values >1.5/>2/>4/>8 (330/56/18/9 genes respectively). Among these the ‘candidate progression genes’ of interest include CD24, SERPIN A1, palladin, protocadherin 9, insulin-receptor, SMURF1, RERG, RUNX1T1, ST14, PDGFRL, osteonectin, APRIN, SSTR1, CHGA, NRCAM, ST18 and SMAD1. Validation of our most promising progression-associated genes on the original frozen tumor samples and larger and independent test sets of archival PETs/PECAs will be presented. Conclusions: We have discovered a novel set of potential progression genes in pancreatic endocrine carcinomas and their synchronous liver metastases. We are currently evaluating the clinical utility of these candidate genes as potential biomarkers of progression in pancreatic endocrine neoplasms. No significant financial relationships to disclose.