Abstract 1980: Transcriptional profiling in peripheral blood mononuclear cells of patients with pancreatic cancer identifies several genes with potential diagnostic and prognostic implications

Abstract

Abstract Background: Pancreatic cancer is one of the most lethal human malignancies, being the fourth most common cause of cancer-related mortality in the Western world and fifth most common worldwide. Despite advancements in understanding the pathogenesis of this malignancy, no reliable screening test currently exists for pancreatic cancer. As a result, the majority of patients present with advanced stage disease contributing to a poor prognosis. Owing to their accessibility, peripheral blood mononuclear cells (PBMCs) are a rich source of potential biomarkers for diagnosis and predicting patient outcome. The question of whether the gene expression profile in PBMCs of pancreatic cancer patients could be useful for its detection has not been examined. Hence, we tested the hypothesis that global gene expression profiling of PBMCs from pancreatic cancer patients could be useful to identify genes potentially useful as specific, early, surrogate biomarkers in the diagnosis of lethal pancreatic cancer. Experimental design: We evaluated the transcriptional profile in PBMCs of 35 patients with pancreatic adenocarcinoma and compared it to that of 33 healthy controls using a Phalanx whole genome microarray containing probes for 39,200 genes. The Universal human reference was used as the reference against which all samples were normalized. We further validated the results of the microarray by quantitative real time PCR using SYBR green based chemistry. The normalization of the data was performed using the BRB Array tool software (http://linus.nci.nih.gov/BRB-ArrayTools.html) Results: After normalization and filtering the genes (criteria: false discovery rate <10%, confidence level 90%), 21,671 genes remained for analysis. 530 genes were found to be differentially expressed in pancreatic cancer patients (p<0.05). 78 of these genes had at least a 1.5 fold change (up or down-regulation) in expression compared to that in the control PBMCs. The expression of two significantly upregulated genes (GAPDH, ASGR2) and four significantly down-regulated genes (DYRK2, MS4A1, EDG1, GRAMD1C) were validated via quantitative PCR. There was an 83% correlation between the microarray and qPCR results for these genes. Conclusion: The present study represents the first example of gene expression profiling in the PBMCs of pancreatic cancer patients with the aim of identifying patterns of gene expression for diagnostic and prognostic purposes. 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 1980.