Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Pichler, M; Winter, E; Stotz, M; Eberhard, K; Samonigg, H; Lax, S; Hoefler, G; .
Down-regulation of KRAS-interacting miRNA-143 predicts poor prognosis but not response to EGFR-targeted agents in colorectal cancer.
Br J Cancer. 2012; 106(11):1826-1832
Doi: 10.1038/bjc.2012.175
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Pichler Martin
- Co-Autor*innen der Med Uni Graz
- Eberhard Katharina
- Höfler Gerald
- Samonigg Hellmut
- Stotz Michael
- Winter Elke
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- BACKGROUND: MicroRNA-143 (miRNA-143) is frequently down-regulated in colorectal cancer (CRC) and may influence CRC cell proliferation, apoptosis and sensitivity to 5-fluorouracil. mRNA encoded by the KRAS oncogene has been identified as a target of miRNA-143. However, the prognostic significance of miRNA-143 expression and the ability to predict patient response to epidermal growth factor receptor (EGFR)-targeted agents have not yet been explored. METHODS: We examined 77 CRC patients who were identified by pyrosequencing to have wild-type KRAS and were subsequently treated with EGFR-targeted therapy with the monoclonal antibodies cetuximab or panitumumab. MicroRNA-143 expression was measured in CRC tissue and corresponding non-neoplastic colon tissue by RT-PCR and its expression level was correlated with clinico-pathological characteristics. Univariate and multivariate analyses were used to calculate cancer-specific survival (CSS). The progression-free survival (PFS) and objective response rates on EGFR-targeted therapy were also evaluated. RESULTS: Down-regulation of miRNA-143 was observed in 47 out of 77 (61%) tumours. Multivariate Cox regression analysis identified low levels of miRNA-143 expression as an independent prognostic factor with respect to CSS (hazard ratio 1.92, confidence interval = 1.1-3.4, P = 0.024). A significant difference was also observed with regard to PFS on EGFR-targeted therapy (P = 0.031), but there were no significant differences with regard to the objective response rates. CONCLUSION: Our data indicate that miRNA-143 expression levels serve as an independent prognostic biomarker for CRC in KRAS wild-type patients. No role for miRNA-143 expression as a predictive biomarker for EGFR-targeted agents could be identified. Given its negative impact on CSS and PFS, miRNA-143 represents a novel prognosticator and a promising drug target for patients with CRC. British Journal of Cancer (2012) 106, 1826-1832. doi:10.1038/bjc.2012.175 www.bjcancer.com Published online 1 May 2012 (C) 2012 Cancer Research UK
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Antibodies, Monoclonal - therapeutic use
- Antineoplastic Agents - therapeutic use
- Colorectal Neoplasms - drug therapy
- Disease-Free Survival -
- Down-Regulation -
- Drug Resistance, Neoplasm - genetics
- Female -
- Gene Expression Regulation, Neoplastic -
- Humans -
- Kaplan-Meier Estimate -
- Male -
- MicroRNAs - biosynthesis
- Middle Aged -
- Prognosis -
- Proportional Hazards Models -
- Proto-Oncogene Proteins - genetics
- Receptor, Epidermal Growth Factor - metabolism
- Retrospective Studies -
- ras Proteins - genetics
- Find related publications in this database (Keywords)
- microRNA
- colorectal cancer
- prognosis
- KRAS
- targeted therapy