title: Identifying distinct classes of bladder carcinoma using microarrays.
abstract: Bladder cancer is a common malignant disease characterized by frequent recurrences. The stage of disease at diagnosis and the presence of surrounding carcinoma in situ are important in determining the disease course of an affected individual. Despite considerable effort, no accepted immunohistological or molecular markers have been identified to define clinically relevant subsets of bladder cancer. Here we report the identification of clinically relevant subclasses of bladder carcinoma using expression microarray analysis of 40 well characterized bladder tumors. Hierarchical cluster analysis identified three major stages, Ta, T1 and T2-4, with the Ta tumors further classified into subgroups. We built a 32-gene molecular classifier using a cross-validation approach that was able to classify benign and muscle-invasive tumors with close correlation to pathological staging in an independent test set of 68 tumors. The classifier provided new predictive information on disease progression in Ta tumors compared with conventional staging (P < 0.005). To delineate non-recurring Ta tumors from frequently recurring Ta tumors, we analyzed expression patterns in 31 tumors by applying a supervised learning classification methodology, which classified 75% of the samples correctly (P < 0.006). Furthermore, gene expression profiles characterizing each stage and subtype identified their biological properties, producing new potential targets for therapy.
authors.affiliation: Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, DK-8200 Aarhus N, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Dyrskjøt
authors.forename: Thomas
authors.initials: T
authors.lastname: Thykjaer
authors.forename: Mogens
authors.initials: M
authors.lastname: Kruhøffer
authors.forename: Jens Ledet
authors.initials: JL
authors.lastname: Jensen
authors.forename: Niels
authors.initials: N
authors.lastname: Marcussen
authors.forename: Stephen
authors.initials: S
authors.lastname: Hamilton-Dutoit
authors.forename: Hans
authors.initials: H
authors.lastname: Wolf
authors.forename: Torben F
authors.initials: TF
authors.lastname: Orntoft
mesh_terms: D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D015203:Reproducibility of Results; D001749:Urinary Bladder Neoplasms / Q000145:classification* / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm