title: MiRNA expression in urothelial carcinomas: important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31.
abstract: We analyzed 34 cases of urothelial carcinomas by miRNA, mRNA and genomic profiling. Unsupervised hierarchical clustering using expression information for 300 miRNAs produced 3 major clusters of tumors corresponding to Ta, T1 and T2-T3 tumors, respectively. A subsequent SAM analysis identified 51 miRNAs that discriminated the 3 pathological subtypes. A score based on the expression levels of the 51 miRNAs, identified muscle invasive tumors with high precision and sensitivity. MiRNAs showing high expression in muscle invasive tumors included miR-222 and miR-125b and in Ta tumors miR-10a. A miRNA signature for FGFR3 mutated cases was also identified with miR-7 as an important member. MiR-31, located in 9p21, was found to be homozygously deleted in 3 cases and miR-452 and miR-452* were shown to be over expressed in node positive tumors. In addition, these latter miRNAs were shown to be excellent prognostic markers for death by disease as outcome. The presented data shows that pathological subtypes of urothelial carcinoma show distinct miRNA gene expression signatures.
authors.affiliation: Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Veerla
authors.forename: David
authors.initials: D
authors.lastname: Lindgren
authors.forename: Anders
authors.initials: A
authors.lastname: Kvist
authors.forename: Attila
authors.initials: A
authors.lastname: Frigyesi
authors.forename: Johan
authors.initials: J
authors.lastname: Staaf
authors.forename: Helena
authors.initials: H
authors.lastname: Persson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Liedberg
authors.forename: Gunilla
authors.initials: G
authors.lastname: Chebil
authors.forename: Sigurdur
authors.initials: S
authors.lastname: Gudjonsson
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
authors.forename: Wiking
authors.initials: W
authors.lastname: Månsson
authors.forename: Carlos
authors.initials: C
authors.lastname: Rovira
authors.forename: Mattias
authors.initials: M
authors.lastname: Höglund
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006720:Homozygote; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D019042:Muscle Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011971:Receptors, Immunologic / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C491341:LILRB2 protein, human; C531888:MIRN125 microRNA, human; C534612:MIRN31 microRNA, human; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D011971:Receptors, Immunologic