Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma

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Authors

MLČOCHOVÁ Hana MACHÁČKOVÁ Táňa RABIEN Anja RADOVÁ Lenka FABIAN Pavel ILIEV Robert SLABÁ Kateřina POPRACH Alexandr KILIC Ergin STANIK Michal LOJOVÁ Martina SVOBODA Marek DOLEZEL Jan VYZULA Rostislav JUNG Klaus SLABÝ Ondřej

Year of publication 2016
Type Article in Periodical
Magazine / Source Scientific Reports
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994011/pdf/srep31852.pdf
Doi http://dx.doi.org/10.1038/srep31852
Field Oncology and hematology
Keywords CANCER; GENE; EXPRESSION; PATHWAYS; TARGETS; PROTEIN; FREM1
Description 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.
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