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miR-181a is associated with poor clinical outcome in patients with colorectal cancer treated with EGFR inhibitor
  1. Martin Pichler1,
  2. Elke Winter2,
  3. Anna Lena Ress1,
  4. Thomas Bauernhofer1,
  5. Armin Gerger1,
  6. Tobias Kiesslich3,
  7. Sigurd Lax4,
  8. Hellmut Samonigg1,
  9. Gerald Hoefler2
  1. 1Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria
  2. 2Institute of Pathology, Medical University of Graz (MUG), Graz, Austria
  3. 3Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria
  4. 4Department of Pathology, General Hospital Graz West, Graz, Austria
  1. Correspondence to Dr Martin Pichler, Medical University of Graz (MUG), Division of Clinical Oncology, Auenbruggerplatz 15, Graz A-8036, Austria; martin.pichler{at}medunigraz.at

Abstract

Aims 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.

Methods 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.

Results 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).

Conclusions 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.

  • CANCER RESEARCH
  • COLORECTAL CANCER
  • CANCER

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