title: MicroRNA Expression Profile Identifies High Grade, Non-Muscle-Invasive Bladder Tumors at Elevated Risk to Progress to an Invasive Phenotype.
abstract: The objective of this study was to identify a panel of microRNAs (miRNAs) differentially expressed in high-grade non-muscle invasive (NMI; TaG3-T1G3) urothelial carcinoma that progress to muscle-invasive disease compared to those that remain non-muscle invasive, whether recurrence happens or not. Eighty-nine high-grade NMI urothelial carcinoma lesions were identified and total RNA was extracted from paraffin-embedded tissue. Patients were categorized as either having a non-muscle invasive lesion with no evidence of progression over a 3-year period or as having a similar lesion showing progression to muscle invasion over the same period. In addition, comparison of miRNA expression levels between patients with and without prior intravesical therapy was performed. Total RNA was pooled for microarray analysis in each group (non-progressors and progressors), and qRT-PCR of individual samples validated differential expression between non-progressive and progressive lesions. MiR-32-5p, -224-5p, and -412-3p were associated with cancer-specific survival. Downregulation of miR-203a-3p and miR-205-5p were significantly linked to progression in non-muscle invasive bladder tumors. These miRNAs include those implicated in epithelial mesenchymal transition, previously identified as members of a panel characterizing transition from the non-invasive to invasive phenotype in bladder tumors. Furthermore, we were able to identify specific miRNAs that are linked to postoperative outcome in patients with high grade NMI urothelial carcinoma of the bladder (UCB) that progressed to muscle-invasive (MI) disease.
authors.affiliation: Department of Urology, Lahey Hospital and Medical Center, Burlington, MA 01805, USA. sara.lenherr@hsc.utah.edu.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Lenherr
authors.affiliation: Department of Urology, Lahey Hospital and Medical Center, Burlington, MA 01805, USA. stsai@winhosp.org.
authors.forename: Sheaumei
authors.initials: S
authors.lastname: Tsai
authors.affiliation: Department of Urology, Lahey Hospital and Medical Center, Burlington, MA 01805, USA. bneto@hcpa.edu.br.|Department of Urology, Hospital de Clinicas de Porto Alegre, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, Brazil. bneto@hcpa.edu.br.
authors.forename: Brasil
authors.initials: B
authors.lastname: Silva Neto
authors.affiliation: Cell and Molecular Biology Laboratory, Lahey Hospital and Medical Center, Burlington, MA 01805, USA. Travis.B.Sullivan@lahey.org.
authors.forename: Travis B
authors.initials: TB
authors.lastname: Sullivan
authors.affiliation: Department of Urology, Lahey Hospital and Medical Center, Burlington, MA 01805, USA. ccimmin@emory.edu.
authors.forename: Cara B
authors.initials: CB
authors.lastname: Cimmino
authors.affiliation: Biostatistics Research, Institute for Clinical Research Health Policy Studies, Tufts Medical Center, Boston, MA 02111, USA. Tanya.Logvinenko@childrens.harvard.edu.
authors.forename: Tanya
authors.initials: T
authors.lastname: Logvinenko
authors.affiliation: Department of Urology, Lahey Hospital and Medical Center, Burlington, MA 01805, USA. Jason.R.Gee@lahey.org.
authors.forename: Jason
authors.initials: J
authors.lastname: Gee
authors.affiliation: Department of Pathology, University of Wisconsin, Madison, WI 53726, USA. WHuang@uwhealth.org.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Urology, Lahey Hospital and Medical Center, Burlington, MA 01805, USA. John.A.Libertino@lahey.org.
authors.forename: John A
authors.initials: JA
authors.lastname: Libertino
authors.affiliation: Department of Urology, Lahey Hospital and Medical Center, Burlington, MA 01805, USA. Ian.C.Summerhayes@lahey.org.|Cell and Molecular Biology Laboratory, Lahey Hospital and Medical Center, Burlington, MA 01805, USA. Ian.C.Summerhayes@lahey.org.|Deceased. Ian.C.Summerhayes@lahey.org.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Summerhayes
authors.affiliation: Department of Urology, Lahey Hospital and Medical Center, Burlington, MA 01805, USA. Kimberly.R.Christ@lahey.org.|Cell and Molecular Biology Laboratory, Lahey Hospital and Medical Center, Burlington, MA 01805, USA. Kimberly.R.Christ@lahey.org.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Rieger-Christ
keywords: intravesical therapy; microRNA; non-muscle invasive bladder cancer; progression