EPITHELIAL-MESENCHYMAL TRANSITION-ASSOCIATED MICRORNA/MRNA SIGNATURE IS LINKED TO METASTASIS AND PROGNOSIS IN CLEAR-CELL RENAL CELL CARCINOMA

Varování

Publikace nespadá pod Lékařskou fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.

Autoři	MLČOCHOVÁ Hana SLABÝ Ondřej MACHÁČKOVÁ Táňa RABIEN Anja RADOVÁ Lenka FABIAN Pavel SLABÁ Kateřina POPRACH Alexandr KILIC Ergin JUNG Klaus
Rok publikování	2016
Druh	Konferenční abstrakty
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
Popis	Purpose: The aim of our study was to identify an integrated microRNA/mRNA signature as sociated with metastasis and prognosis in clear-cell renal cell carcinoma (ccRCC) through targeted approach based on analysis of microRNAs/mRNAs as sociated with epithelialmesenchymal transition (EMT). Experimental Design: A cohort of 230 ccRCC was included in our study and further divided into discovery, train ing and validation cohorts. EMT markers (CDH1, CK18, CK19, VIM, S100A4) were evaluated in ccRCC tumor samples, which were grouped accordingly to EMT status, and large-scale miRNA/ mRNA expression profiling was performed on exploratory cohorts to identify EMT-associated miRNAs/mRNAs. Diagnostic and prognostic potential of these miRNA s/mRNAs was evaluated on independent train ing and validation cohorts. Results: We identifi ed miRNA/ mRNA profiles 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 forwarded to validation phase, where 15 was confirmed to be significantly deregulated in tumor tissue (all p < 0.0001), 11 significantly differed in metastatic and non-metastatic tumors, 12 significantly correlated with clinical stage, 11 with Fuhrman grade and 9 with overall survival. Further, we have established an EMT-based stage-independent prognostic scoring system (miR-200a, miR-200b, miR-200c, miR-30a-3p, miR-429, CDH1, C3orf52 and PAP SS2) enabling identification of RCC patients at high-risk of cancer-related death (HR 3.63, 95% CI 1.69– 7.81; p < 0.001). Finally, we confirmed functioning of miR-429 in EMT regulation in RCC cells in vitro. Conclusion: EMT-targeted approach enabled identifi cation of novel miRNAs/mRNAs as sociated with metastasis and prognosis and development of stage-independent prognostic model in ccRCC.