title: Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma.
abstract: Clear-cell renal cell carcinomas (ccRCCs) are genetically heterogeneous tumors presenting diverse clinical courses. Epithelial-mesenchymal transition (EMT) is a crucial process involved in initiation of metastatic cascade. The aim of our study was to identify an integrated miRNA/mRNA signature associated with metastasis and prognosis in ccRCC through targeted approach based on analysis of miRNAs/mRNAs associated with EMT. A cohort of 230 ccRCC was included in our study and further divided into discovery, training and validation cohorts. EMT markers were evaluated in ccRCC tumor samples, which were grouped accordingly to EMT status. By use of large-scale miRNA/mRNA expression profiling, we identified miRNA/mRNA with significantly different expression in EMT-positive tumors and selected 41 miRNAs/mRNAs for training phase of the study to evaluate their diagnostic and prognostic potential. Fifteen miRNAs/mRNAs were analyzed in the validation phase, where all evaluated miRNA/mRNA candidates were confirmed to be significantly deregulated in tumor tissue. Some of them significantly differed in metastatic tumors, correlated with clinical stage, with Fuhrman grade and with overall survival. Further, we established an EMT-based stage-independent prognostic scoring system enabling identification of ccRCC patients at high-risk of cancer-related death. Finally, we confirmed involvement of miR-429 in EMT regulation in RCC cells in vitro.
authors.affiliation: Masaryk University, Central European Institute of Technology (CEITEC), Kamenice 5, 625 00, Brno, Czech Republic.|Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Zluty kopec 7, 656 53, Brno, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Mlcochova
authors.affiliation: Masaryk University, Central European Institute of Technology (CEITEC), Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Tana
authors.initials: T
authors.lastname: Machackova
authors.affiliation: University Hospital Charite, Humboldt University, Department of Urology, Schumannstrasse 20/21, D-10117 Berlin, Germany.|Berlin Institute for Urologic Research, Robert-Koch Platz 7, 10115 Berlin, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Rabien
authors.affiliation: Masaryk University, Central European Institute of Technology (CEITEC), Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Radova
authors.affiliation: Masaryk Memorial Cancer Institute, Department of Diagnostic and Experimental Pathology, Zluty kopec 7, 656 53, Brno, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Fabian
authors.affiliation: Masaryk University, Central European Institute of Technology (CEITEC), Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Robert
authors.initials: R
authors.lastname: Iliev
authors.affiliation: Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Zluty kopec 7, 656 53, Brno, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Slaba
authors.affiliation: Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Zluty kopec 7, 656 53, Brno, Czech Republic.
authors.forename: Alexandr
authors.initials: A
authors.lastname: Poprach
authors.affiliation: University Hospital Charite, Humboldt University, Institute of Pathology, Schumannstrasse 20/21, D-10117 Berlin, Germany.
authors.forename: Ergin
authors.initials: E
authors.lastname: Kilic
authors.affiliation: Masaryk Memorial Cancer Institute, Department of Urologic Oncology, Zluty kopec 7, 656 53, Brno, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Stanik
authors.affiliation: Masaryk University, Central European Institute of Technology (CEITEC), Kamenice 5, 625 00, Brno, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Redova-Lojova
authors.affiliation: Masaryk University, Central European Institute of Technology (CEITEC), Kamenice 5, 625 00, Brno, Czech Republic.|Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Zluty kopec 7, 656 53, Brno, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Svoboda
authors.affiliation: Masaryk Memorial Cancer Institute, Department of Urologic Oncology, Zluty kopec 7, 656 53, Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Dolezel
authors.affiliation: Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Zluty kopec 7, 656 53, Brno, Czech Republic.
authors.forename: Rostislav
authors.initials: R
authors.lastname: Vyzula
authors.affiliation: University Hospital Charite, Humboldt University, Department of Urology, Schumannstrasse 20/21, D-10117 Berlin, Germany.|Berlin Institute for Urologic Research, Robert-Koch Platz 7, 10115 Berlin, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.affiliation: Masaryk University, Central European Institute of Technology (CEITEC), Kamenice 5, 625 00, Brno, Czech Republic.|Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Zluty kopec 7, 656 53, Brno, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Slaby
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D016019:Survival Analysis
chemical_list: C546363:MIRN429 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger