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.

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T1 - 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.

AU - Veerla, Srinivas

AU - Lindgren, David

AU - Kvist, Anders

AU - Frigyesi, Attila

AU - Staaf, Johan

AU - Persson, Helena

AU - Liedberg, Fredrik

AU - Chebil, Gunilla

AU - Gudjonsson, Sigurdur

AU - Borg, Åke

AU - Månsson, Wiking

AU - Rovira, Carlos

AU - Höglund, Mattias

PY - 2009

Y1 - 2009

N2 - 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. (c) 2009 Wiley-Liss, Inc.

AB - 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. (c) 2009 Wiley-Liss, Inc.

U2 - 10.1002/ijc.24183

DO - 10.1002/ijc.24183

M3 - Article

VL - 124

SP - 2236

EP - 2242

JO - Acta - Unio Internationalis Contra Cancrum

T2 - Acta - Unio Internationalis Contra Cancrum

JF - Acta - Unio Internationalis Contra Cancrum

SN - 0020-7136

ER -