%0 Journal Article
%T Expression profiling in canine osteosarcoma: identification of biomarkers and pathways associated with outcome
%A Liza E O'Donoghue
%A Andrey A Ptitsyn
%A Debra A Kamstock
%A Janet Siebert
%A Russell S Thomas
%A Dawn L Duval
%J BMC Cancer
%D 2010
%I BioMed Central
%R 10.1186/1471-2407-10-506
%X We analyzed archived primary OSA tissue from dogs treated with limb amputation followed by doxorubicin or platinum-based drug chemotherapy. Samples were selected from two groups: dogs with disease free intervals (DFI) of less than 100 days (n = 8) and greater than 300 days (n = 7). Gene expression was assessed with Affymetrix Canine 2.0 microarrays and analyzed with a two-tailed t-test. A subset of genes was confirmed using qRT-PCR and used in classification analysis to predict prognosis. Systems-based gene ontology analysis was conducted on genes selected using a standard J5 metric. The genes identified using this approach were converted to their human homologues and assigned to functional pathways using the GeneGo MetaCore platform.Potential biomarkers were identified using gene expression microarray analysis and 11 differentially expressed (p < 0.05) genes were validated with qRT-PCR (n = 10/group). Statistical classification models using the qRT-PCR profiles predicted patient outcomes with 100% accuracy in the training set and up to 90% accuracy upon stratified cross validation. Pathway analysis revealed alterations in pathways associated with oxidative phosphorylation, hedgehog and parathyroid hormone signaling, cAMP/Protein Kinase A (PKA) signaling, immune responses, cytoskeletal remodeling and focal adhesion.This profiling study has identified potential new biomarkers to predict patient outcome in OSA and new pathways that may be targeted for therapeutic intervention.Osteosarcoma (OSA) is the most common malignant primary bone tumor of children and accounts for roughly 5% of all childhood cancers in the United States. Characteristically, OSA is found in the metaphyseal regions of long bones in the appendicular skeleton. More than 15% of patients present with clinically detectable pulmonary metastases and it is estimated that 80% or more have micrometastases at presentation [1]. Advances in treatment such as multi-agent chemotherapy have improved prognosis ove
%U http://www.biomedcentral.com/1471-2407/10/506