Differential expression of metabolic genes in tumor and stromal components in primary and metastatic loci in pancreatic adenocarcinomas

ABSTRACT: Background:Pancreatic cancer is the fourth leading cause of cancer related deaths the United States with a five-year survival rate of 6% (1). It is characterized by extremely aggressive tumor growth rate and high incidence of metastasis. One of the most common and profound biochemical phenotypes of animal and human cancer cells is their ability to metabolize glucose at high rates, even under aerobic conditions (2-5). However, the contribution of metabolic interrelationships between tumor cells and cells of the surrounding microenvironment to the progression of cancer is not well understood. We evaluated differential expression of metabolic genes and hence, metabolic pathways in primary tumor and metastases of patients with pancreatic adenocarcinoma. Methods and Findings:We analyzed the metabolic gene (those involved in glycolysis, tri-carboxylic acid pathway, pentose-phosphate pathway and fatty acid metabolism) expression profiles of primary and metastatic lesions from 35 pancreatic cancer patients by Affymetrix expression arrays. We observed two principal results: genes that were upregulated in primary and most of the metastatic lesions; and genes that were upregulated only in specific metastatic lesions in a site-specific manner. Immunohistochemical (IHC) analyses of several metabolic gene products confirmed the gene expression patterns at the protein level. The IHC analyses also revealed differential tumor and stromal expression patterns of metabolic enzymes that were correlated with the metastasis sites. Conclusions: Here, we present the first comprehensive studies that establish differential metabolic status of tumor and stromal components and elevation of aerobic glycolysis gene expression in pancreatic cancer. Furthermore, we identify key metabolic genes that can be targeted to diminish overall cancer progression and others that can be targeted to prevent cancer metastasis at specific organ sites.

ORGANISM(S): Homo sapiens

PROVIDER: GSE34153 | GEO | 2012/04/29

SECONDARY ACCESSION(S): PRJNA150047

REPOSITORIES: GEO