title: A CD133-related gene expression signature identifies an aggressive glioblastoma subtype with excessive mutations.
abstract: Cancer cells are heterogeneous and, it has been proposed, fall into at least two classes: the tumor-initiating cancer stem cells (CSC) and the more differentiated tumor cells. The transmembrane protein CD133 has been widely used to isolate putative CSC populations in several cancer types, but its validity as a CSC marker and hence its clinical ramifications remain controversial. Here, we conducted transcriptomic profiling of sorted CD133(+) and CD133(-) cells from human glioblastoma multiforme (GBM) and, by subtractive analysis, established a CD133 gene expression signature composed of 214 differentially expressed genes. Extensive computational comparisons with a compendium of published gene expression profiles reveal that the CD133 gene signature transcriptionally resembles human ES cells and in vitro cultured GBM stem cells, and this signature successfully distinguishes GBM from lower-grade gliomas. More importantly, the CD133 gene signature identifies an aggressive subtype of GBM seen in younger patients with shorter survival who bear excessive genomic mutations as surveyed through the Cancer Genome Atlas Network GBM mutation spectrum. Furthermore, the CD133 gene signature distinguishes higher-grade breast and bladder cancers from their lower-grade counterparts. Our systematic analysis provides molecular and genetic support for the stem cell-like nature of CD133(+) cells and an objective means for evaluating cancer aggressiveness.
authors.affiliation: Institute for Systems Biology, Seattle, WA 98103, USA.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Yan
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Danielle
authors.initials: D
authors.lastname: Yi
authors.forename: Jae-geun
authors.initials: JG
authors.lastname: Yoon
authors.forename: Alan
authors.initials: A
authors.lastname: Diercks
authors.forename: Gregory
authors.initials: G
authors.lastname: Foltz
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Price
authors.forename: Leroy E
authors.initials: LE
authors.lastname: Hood
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tian
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D016000:Cluster Analysis; D053595:Embryonic Stem Cells / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D014411:Neoplastic Stem Cells / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides