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
