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

a 2016

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

MLČOCHOVÁ, Hana; Ondřej SLABÝ; Táňa MACHÁČKOVÁ; Anja RABIEN; Lenka RADOVÁ et. al.

Základní údaje

Originální název

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

Autoři

MLČOCHOVÁ, Hana; Ondřej SLABÝ; Táňa MACHÁČKOVÁ; Anja RABIEN; Lenka RADOVÁ; Pavel FABIAN; Kateřina SLABÁ; Alexandr POPRACH; Ergin KILIC a Klaus JUNG

Vydání

XL. brněnské onkologické dny a XXX. koncerence pro nelékařské zdravotnické pracovníky, Brno, 2016

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Organizační jednotka

Středoevropský technologický institut

ISSN

Klíčová slova česky

miRNA; mRNA; epiteliálně-mezenchymální tranzice; renální karcinom

Změněno: 4. 5. 2016 10:56, Mgr. Petra Vychytilová, Ph.D.

Anotace

V originále

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.

Citovat

MLČOCHOVÁ, Hana; Ondřej SLABÝ; Táňa MACHÁČKOVÁ; Anja RABIEN; Lenka RADOVÁ; Pavel FABIAN; Kateřina SLABÁ; Alexandr POPRACH; Ergin KILIC a Klaus JUNG. EPITHELIAL-MESENCHYMAL TRANSITION-ASSOCIATED MICRORNA/MRNA SIGNATURE IS LINKED TO METASTASIS AND PROGNOSIS IN CLEAR-CELL RENAL CELL CARCINOMA. In XL. brněnské onkologické dny a XXX. koncerence pro nelékařské zdravotnické pracovníky, Brno. 2016. ISSN 0862-495X.

@proceedings{1344250,
   author = {Mlčochová, Hana and Slabý, Ondřej and Macháčková, Táňa and Rabien, Anja and Radová, Lenka and Fabian, Pavel and Slabá, Kateřina and Poprach, Alexandr and Kilic, Ergin and Jung, Klaus},
   booktitle = {XL. brněnské onkologické dny a XXX. koncerence pro nelékařské zdravotnické pracovníky, Brno},
   language = {eng},
   title = {EPITHELIAL-MESENCHYMAL TRANSITION-ASSOCIATED MICRORNA/MRNA SIGNATURE IS LINKED TO METASTASIS AND PROGNOSIS IN CLEAR-CELL RENAL CELL CARCINOMA},
   year = {2016}
}

TY  - CONF
ID  - 1344250
AU  - Mlčochová, Hana - Slabý, Ondřej - Macháčková, Táňa - Rabien, Anja - Radová, Lenka - Fabian, Pavel - Slabá, Kateřina - Poprach, Alexandr - Kilic, Ergin - Jung, Klaus
PY  - 2016
TI  - EPITHELIAL-MESENCHYMAL TRANSITION-ASSOCIATED MICRORNA/MRNA SIGNATURE IS LINKED TO METASTASIS AND PROGNOSIS IN CLEAR-CELL RENAL CELL CARCINOMA
N2  - 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.
ER  -

MLČOCHOVÁ, Hana; Ondřej SLABÝ; Táňa MACHÁČKOVÁ; Anja RABIEN; Lenka RADOVÁ; Pavel FABIAN; Kateřina SLABÁ; Alexandr POPRACH; Ergin KILIC a Klaus JUNG. EPITHELIAL-MESENCHYMAL TRANSITION-ASSOCIATED MICRORNA/MRNA SIGNATURE IS LINKED TO METASTASIS AND PROGNOSIS IN CLEAR-CELL RENAL CELL CARCINOMA. In \textit{XL. brněnské onkologické dny a XXX. koncerence pro nelékařské zdravotnické pracovníky, Brno}. 2016. ISSN~0862-495X.

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