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@article{1411964,
author = {Pichler, M. and Stiegelbauer, V. and Vychytilová, Petra and Ivan, C. and Ling, H. and Winter, E. and Zhang, X.N. and Goblirsch, M. and WulfandGoldenberg, A. and Ohtsuka, M. and Haybaeck, J. and Svoboda, M. and Okugawa, Y. and Gerger, A. and Hoefler, G. and Goel, A. and Slabý, Ondřej and Calin, G.A.},
article_location = {Philadelphia},
article_number = {5},
doi = {http://dx.doi.org/10.1158/1078-0432.CCR-16-0497},
keywords = {ANTI-EGFR THERAPY; TUMOR-GROWTH; COLON-CANCER; MICRORNA SIGNATURES; PREDICTIVE-VALUE; STAGE-II; METASTASIS; EXPRESSION; PROGRESSION; BIOMARKER},
language = {eng},
issn = {1078-0432},
journal = {Clinical cancer research},
title = {Genome-Wide miRNA Analysis Identifies miR-188-3p as a Novel Prognostic Marker and Molecular Factor Involved in Colorectal Carcinogenesis},
url = {http://clincancerres.aacrjournals.org/content/23/5/1323},
volume = {23},
year = {2017}
}
TY - JOUR
ID - 1411964
AU - Pichler, M. - Stiegelbauer, V. - Vychytilová, Petra - Ivan, C. - Ling, H. - Winter, E. - Zhang, X.N. - Goblirsch, M. - Wulf-Goldenberg, A. - Ohtsuka, M. - Haybaeck, J. - Svoboda, M. - Okugawa, Y. - Gerger, A. - Hoefler, G. - Goel, A. - Slabý, Ondřej - Calin, G.A.
PY - 2017
TI - Genome-Wide miRNA Analysis Identifies miR-188-3p as a Novel Prognostic Marker and Molecular Factor Involved in Colorectal Carcinogenesis
JF - Clinical cancer research
VL - 23
IS - 5
SP - 1323-1333
EP - 1323-1333
PB - AMER ASSOC CANCER RESEARCH
SN - 10780432
KW - ANTI-EGFR THERAPY
KW - TUMOR-GROWTH
KW - COLON-CANCER
KW - MICRORNA SIGNATURES
KW - PREDICTIVE-VALUE
KW - STAGE-II
KW - METASTASIS
KW - EXPRESSION
KW - PROGRESSION
KW - BIOMARKER
UR - http://clincancerres.aacrjournals.org/content/23/5/1323
L2 - http://clincancerres.aacrjournals.org/content/23/5/1323
N2 - Purpose: Characterization of colorectal cancer transcriptome by high-throughput techniques has enabled the discovery of several differentially expressed genes involving previously unreported miRNA abnormalities. Here, we followed a systematic approach on a global scale to identify miRNAs as clinical outcome predictors and further validated them in the clinical and experimental setting. Experimental Design: Genome-wide miRNA sequencing data of 228 colorectal cancer patients from The Cancer Genome Atlas dataset were analyzed as a screening cohort to identify miRNAs significantly associated with survival according to stringent pre-specified criteria. A panel of six miRNAs was further validated for their prognostic utility in a large independent validation cohort (n = 332). In situ hybridization and functional experiments in a panel of colorectal cancer cell lines and xenografts further clarified the role of clinical relevant miRNAs. Results: SixmiRNAs (miR-92b-3p, miR-188-3p, miR-221-5p, miR-331-3p, miR-425-3p, and miR-497-5p) were identified as strong predictors of survival in the screening cohort. High miR-188-3p expression proves to be an independent prognostic factor [screening cohort: HR = 4.137; 95% confidence interval (CI), 1.568-10.917; P = 0.004; validation cohort: HR = 1.538; 95% CI, 1.107-2.137; P = 0.010, respectively]. Forced miR-188-3p expression increased migratory behavior of colorectal cancer cells in vitro and metastases formation in vivo (P < 0.05). The promigratory role of miR-188-3p is mediated by direct interaction with MLLT4, a novel identified player involved in colorectal cancer cell migration. Conclusions: miR-188-3p is a novel independent prognostic factor in colorectal cancer patients, which can be partly explained by its effect on MLLT4 expression and migration of cancer cells. (C) 2016 AACR.
ER -
PICHLER, M., V. STIEGELBAUER, Petra VYCHYTILOVÁ, C. IVAN, H. LING, E. WINTER, X.N. ZHANG, M. GOBLIRSCH, A. WULF-GOLDENBERG, M. OHTSUKA, J. HAYBAECK, M. SVOBODA, Y. OKUGAWA, A. GERGER, G. HOEFLER, A. GOEL, Ondřej SLABÝ and G.A. CALIN. Genome-Wide miRNA Analysis Identifies miR-188-3p as a Novel Prognostic Marker and Molecular Factor Involved in Colorectal Carcinogenesis. \textit{Clinical cancer research}. Philadelphia: AMER ASSOC CANCER RESEARCH, 2017, vol.~23, No~5, p.~1323-1333. ISSN~1078-0432. Available from: https://dx.doi.org/10.1158/1078-0432.CCR-16-0497.
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