2017
Genome-Wide miRNA Analysis Identifies miR-188-3p as a Novel Prognostic Marker and Molecular Factor Involved in Colorectal Carcinogenesis
PICHLER, M., V. STIEGELBAUER, Petra VYCHYTILOVÁ, C. IVAN, H. LING et. al.Základní údaje
Originální název
Genome-Wide miRNA Analysis Identifies miR-188-3p as a Novel Prognostic Marker and Molecular Factor Involved in Colorectal Carcinogenesis
Autoři
PICHLER, M. (40 Rakousko), V. STIEGELBAUER (40 Rakousko), Petra VYCHYTILOVÁ (203 Česká republika, domácí), C. IVAN (40 Rakousko), H. LING (40 Rakousko), E. WINTER (40 Rakousko), X.N. ZHANG (840 Spojené státy), M. GOBLIRSCH (40 Rakousko), A. WULF-GOLDENBERG (276 Německo), M. OHTSUKA (840 Spojené státy), J. HAYBAECK (840 Spojené státy), M. SVOBODA (203 Česká republika), Y. OKUGAWA (840 Spojené státy), A. GERGER (840 Spojené státy), G. HOEFLER (40 Rakousko), A. GOEL (840 Spojené státy), Ondřej SLABÝ (203 Česká republika, garant, domácí) a G.A. CALIN (840 Spojené státy)
Vydání
Clinical cancer research, Philadelphia, AMER ASSOC CANCER RESEARCH, 2017, 1078-0432
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30204 Oncology
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 10.199
Kód RIV
RIV/00216224:14740/17:00100443
Organizační jednotka
Středoevropský technologický institut
UT WoS
000396015600023
Klíčová slova anglicky
ANTI-EGFR THERAPY; TUMOR-GROWTH; COLON-CANCER; MICRORNA SIGNATURES; PREDICTIVE-VALUE; STAGE-II; METASTASIS; EXPRESSION; PROGRESSION; BIOMARKER
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 26. 4. 2021 13:41, Mgr. Tereza Miškechová
Anotace
V originále
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.
Návaznosti
ED1.1.00/02.0068, projekt VaV |
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90004, velká výzkumná infrastruktura |
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