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.
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.
Veerla
Srinivas
S
Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
Lindgren
David
D
Kvist
Anders
A
Frigyesi
Attila
A
Staaf
Johan
J
Persson
Helena
H
Liedberg
Fredrik
F
Chebil
Gunilla
G
Gudjonsson
Sigurdur
S
Borg
Ake
A
Månsson
Wiking
W
Rovira
Carlos
C
Höglund
Mattias
M
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
C491341:LILRB2 protein, human; C531888:MIRN125 microRNA, human; C534612:MIRN31 microRNA, human; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D011971:Receptors, Immunologic