title: Progression-associated genes in astrocytoma identified by novel microarray gene expression data reanalysis.
abstract: Astrocytoma is graded as pilocytic (WHO grade I), diffuse (WHO grade II), anaplastic (WHO grade III), and glioblastoma multiforme (WHO grade IV). The progression from low- to high-grade astrocytoma is associated with distinct molecular changes that vary with patient age, yet the prognosis of high-grade tumors in children and adults is equally dismal. Whether specific gene expression changes are consistently associated with all high-grade astrocytomas, independent of patient age, is not known. To address this question, we reanalyzed the microarray datasets comprising astrocytomas from children and adults, respectively. We identified nine genes consistently dysregulated in high-grade tumors, using four novel tests for identifying differentially expressed genes. Four genes encoding ribosomal proteins (RPS2, RPS8, RPS18, RPL37A) were upregulated, and five genes (APOD, SORL1, SPOCK2, PRSS11, ID3) were downregulated in high-grade by all tests. Expression results were validated using a third astrocytoma dataset. APOD, the most differentially expressed gene, has been shown to inhibit tumor cell and vascular smooth muscle cell proliferation. This suggests that dysregulation of APOD may be critical for malignant astrocytoma formation, and thus a possible novel universal target for therapeutic intervention. Further investigation is needed to evaluate the role of APOD, as well as the other genes identified, in malignant astrocytoma development.
authors.affiliation: Center for Cancer and Immunology Research, Children's Research Institute, Department of Hematology-Oncology, Children's National Medical Center, Washington, DC, USA.
authors.forename: Tobey J
authors.initials: TJ
authors.lastname: MacDonald
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
authors.forename: Hideho
authors.initials: H
authors.lastname: Okada
authors.forename: Soumyaroop
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: James
authors.initials: J
authors.lastname: Lyons-Weiler
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000145:classification / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics*; D002648:Child; D002877:Chromosomes, Human; D016000:Cluster Analysis; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008957:Models, Genetic; D009364:Neoplasm Recurrence, Local; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor