Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Ling, H; Pickard, K; Ivan, C; Isella, C; Ikuo, M; Mitter, R; Spizzo, R; Bullock, M; Braicu, C; Pileczki, V; Vincent, K; Pichler, M; Stiegelbauer, V; Hoefler, G; Almeida, MI; Hsiao, A; Zhang, X; Primrose, J; Packham, G; Liu, K; Bojja, K; Gafà, R; Xiao, L; Rossi, S; Song, JH; Vannini, I; Fanini, F; Kopetz, S; Zweidler-McKay, P; Wang, X; Ionescu, C; Irimie, A; Fabbri, M; Lanza, G; Hamilton, SR; Berindan-Neagoe, I; Medico, E; Mirnezami, A; Calin, GA; Nicoloso, MS.
The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis.
Gut. 2016; 65(6):977-989
Doi: 10.1136/gutjnl-2015-309372
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Höfler Gerald
- Pichler Martin
- Stiegelbauer Verena
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- MicroRNA (miRNA) expression profile can be used as prognostic marker for human cancers. We aim to explore the significance of miRNAs in colorectal cancer (CRC) metastasis. We performed miRNA microarrays using primary CRC tissues from patients with and without metastasis, and validated selected candidates in 85 CRC samples by quantitative real-time PCR (qRT-PCR). We tested metastatic activity of selected miRNAs and identified miRNA targets by prediction algorithms, qRT-PCR, western blot and luciferase assays. Clinical outcomes were analysed in six sets of CRC cases (n=449), including The Cancer Genome Atlas (TCGA) consortium and correlated with miR-224 status. We used the Kaplan-Meier method and log-rank test to assess the difference in survival between patients with low or high levels of miR-224 expression. MiR-224 expression increases consistently with tumour burden and microsatellite stable status, and miR-224 enhances CRC metastasis in vitro and in vivo. We identified SMAD4 as a miR-224 target and observed negative correlation (Spearman Rs=-0.44, p<0.0001) between SMAD4 and miR-224 expression in clinical samples. Patients with high miR-224 levels display shorter overall survival in multiple CRC cohorts (p=0.0259, 0.0137, 0.0207, 0.0181, 0.0331 and 0.0037, respectively), and shorter metastasis-free survival (HR 6.51, 95% CI 1.97 to 21.51, p=0.0008). In the TCGA set, combined analysis of miR-224 with SMAD4 expression enhanced correlation with survival (HR 4.12, 95% CI 1.1 to 15.41, p=0.0175). MiR-224 promotes CRC metastasis, at least in part, through the regulation of SMAD4. MiR-224 expression in primary CRC, alone or combined with its targets, may have prognostic value for survival of patients with CRC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
- Find related publications in this database (using NLM MeSH Indexing)
- Adenocarcinoma - diagnosis
- Adenocarcinoma - genetics
- Adenocarcinoma - mortality
- Adenocarcinoma - secondary
- Adult -
- Aged -
- Aged, 80 and over -
- Animals -
- Austria -
- Biomarkers, Tumor - blood
- Colorectal Neoplasms - diagnosis
- Colorectal Neoplasms - genetics
- Colorectal Neoplasms - mortality
- Colorectal Neoplasms - pathology
- Female -
- Gene Expression Regulation, Neoplastic -
- Humans -
- In Vitro Techniques -
- Italy -
- Kaplan-Meier Estimate -
- Male -
- Mice -
- MicroRNAs - blood
- Middle Aged -
- Neoplasm Invasiveness -
- Predictive Value of Tests -
- Romania -
- Sensitivity and Specificity -
- United Kingdom -