Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Pichler, M; Winter, E; Ress, AL; Bauernhofer, T; Gerger, A; Kiesslich, T; Lax, S; Samonigg, H; Hoefler, G.
miR-181a is associated with poor clinical outcome in patients with colorectal cancer treated with EGFR inhibitor.
J Clin Pathol. 2014; 67(3):198-203 Doi: 10.1136/jclinpath-2013-201904
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Führende Autor*innen der Med Uni Graz
Pichler Martin
Co-Autor*innen der Med Uni Graz
Bauernhofer Thomas
Gerger Armin
Höfler Gerald
Lembeck Anna Lena
Samonigg Hellmut
Winter Elke

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miR-181a expression is frequently altered in different types of cancer. Members of the Wnt/β-catenin signalling pathway, which is commonly altered in colorectal cancer (CRC), have been reported as molecular interaction partners of miR-181. However, the role of miR-181a expression in CRC and its ability to predict survival and response to agents targeting the epidermal growth factor receptor (EGFR) have not been explored yet. In this study, we analysed 80 patients with wild type KRAS CRC undergoing treatment with the EGFR-targeting monoclonal antibodies cetuximab and panitumumab for metastatic CRC. The KRAS mutational status was determined by pyrosequencing and miR-181a expression was measured by quantitative RT-PCR in CRC tumour tissue and corresponding non-neoplastic colon tissue. The microRNA expression levels were correlated with clinicopathological characteristics. Cancer-specific survival was calculated by univariate and multivariate analyses, and progression-free survival (PFS) during treatment with EGFR-targeting agents was also evaluated. A low miR-181a expression level was associated with poor differentiation of CRC (p=0.04). A Kaplan-Meier curve showed a decreased survival time for patients with low miR-181a expression (p=0.019). Low miR-181a expression was furthermore associated with poor PFS (p=0.015). In conclusion, our data suggest that the miR-181a expression level is associated with poor survival in patients with CRC. Furthermore, miR-181a expression might predict PFS in EGFR-targeted therapy.
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Adult -
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Antibodies, Monoclonal - therapeutic use
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Cell Differentiation -
Chi-Square Distribution -
Colorectal Neoplasms - drug therapy
DNA Mutational Analysis -
Disease Progression -
Disease-Free Survival -
Female -
Humans -
Kaplan-Meier Estimate -
Male -
MicroRNAs - metabolism
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Molecular Targeted Therapy -
Multivariate Analysis -
Mutation -
Proportional Hazards Models -
Protein Kinase Inhibitors - therapeutic use
Proto-Oncogene Proteins - genetics
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ras Proteins - genetics

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