Increased Erythropoietin Receptor (EpoR) Expression Is Associated with Distinct Gene Expression Profile in Human Breast Cancer (BC)
Z Rakosy, G Paragh, G Acs. Moffitt Cancer Center, Tampa, FL; Women's Pathology Consultants, Ruffolo Hooper & Associates, Tampa, FL
Background: EpoR serves as a specific receptor for erythropoietin (Epo), a glycoprotein hormone that stimulates the proliferation and inhibits the apoptosis of erythroblasts in the bone marrow. Recombinant human Epo (rHuEpo) has revolutionized the treatment of anemia and is widely used in the management of cancer and therapy related anemia in patients with malignant diseases. Although rHuEpo is effective in correcting anemia and improving quality of life, recent clinical trials suggested that its use may be associated with earlier tumor recurrence/progression and decreased survival. Various human cancer cells were recently shown to express EpoR and in vitro studies suggested that Epo can stimulate signaling mechanisms and proliferation in some cancer cells providing a potential biologic basis for the observed adverse effects rHuEpo in cancer patients. However, currently the role for EpoR in cancer biology is unclear. We investigated whether increased EpoR expression in BC is associated with a distinct gene expression profile in human BC.
Design: Ninety-four macrodissected formalin-fixed paraffin-embedded invasive breast carcinomas were used for microarray analysis using Illumina's cDNA-mediated annealing, selection, extension and ligation (DASL) assay based bead arrays. Based on the expression of EpoR we selected 20 samples each showing the highest and lowest levels of EpoR expression for analysis. Significance Analysis of Microarrays (SAM) and Ingenuity Pathway Analysis software tools were applied for data analysis.
Results: Comparison of whole genome gene expression profiles of tumors with highest and lowest levels of EpoR expression yielded 584 differentially expressed genes at a significance level of p<0.001 and a fold change of >2. Genes (n=414) overexpressed in tumors with high EpoR expression included genes with functional roles in cell cycle regulation and proliferation and hematologic system development and function. Genes with decreased expression mainly play roles in the control of cellular development, movement and cell death. A significant correlation was found between high EpoR expression and estrogen receptor expression in BC (p=0.043).
Conclusions: Our results suggest that high EpoR expression in BC is associated with a distinct gene expression profile compared to tumors with low EpoR expression. Identification of such differentially expressed genes may help understand the biological role of EpoR in the tumor biology.
Monday, March 22, 2010 1:00 PM
Poster Session II # 62, Monday Afternoon