title: Gene-expression-based analysis of local and metastatic neuroblastoma variants reveals a set of genes associated with tumor progression in neuroblastoma patients.
abstract: Metastasis is the primary cause of mortality in Neuroblastoma (NB) patients, but the metastatic process in NB is poorly understood. Metastsis is a multistep process that requires the coordinated action of many genes. The identification of genes that promote or suppress tumor metastasis can advance our understanding of this process. In the present study, we utilized a human NB xenograft model comprising local and metastatic NB variants, which was recently developed in our laboratory. We set out to identify molecular correlates of NB metastasis and to determine the clinical relevance of these molecules. We first performed genome-wide expression profiles of metastatic and nonmetastatic NB variants that have an identical genetic background. We found that some of the proteins highly expressed in the metastatic NB variants are localized in the cytoplasm and endoplasmic reticulum. Other proteins are linked to metabolic processes and signaling pathways, thereby supporting the invasive and metastatic state of the cells. Subsequently, we intersected the differentially expressed genes in the human xenografted variants with genes differentially expressed in Stage 1 and Stage 4 primary tumors of NB patients. By using the same gene-expression platform, molecular correlates associated with metastatic progression in primary NB tumors were identified. The resulting smaller gene set was clinically relevant as it discriminated between high- and low-risk NB patients.
authors.affiliation: Department of Cell Research and Immunology, The George S. Wise Faculty of Life Science, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Nevo
authors.forename: Andre
authors.initials: A
authors.lastname: Oberthuer
authors.forename: Edry
authors.initials: E
authors.lastname: Botzer
authors.forename: Orit
authors.initials: O
authors.lastname: Sagi-Assif
authors.forename: Shelly
authors.initials: S
authors.lastname: Maman
authors.forename: Metsada
authors.initials: M
authors.lastname: Pasmanik-Chor
authors.forename: Naam
authors.initials: N
authors.lastname: Kariv
authors.forename: Matthias
authors.initials: M
authors.lastname: Fischer
authors.forename: Ilana
authors.initials: I
authors.lastname: Yron
authors.forename: Isaac P
authors.initials: IP
authors.lastname: Witz
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D004721:Endoplasmic Reticulum / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D051379:Mice; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D013347:Subcellular Fractions; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor