miR-181a is associated with poor clinical outcome in patients with colorectal cancer treated with EGFR inhibitor

J Clin Pathol. 2014 Mar;67(3):198-203. doi: 10.1136/jclinpath-2013-201904. Epub 2013 Oct 4.

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.

Keywords: CANCER; CANCER RESEARCH; COLORECTAL CANCER.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Cell Differentiation
  • Cetuximab
  • Chi-Square Distribution
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • DNA Mutational Analysis
  • Disease Progression
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Molecular Targeted Therapy
  • Multivariate Analysis
  • Mutation
  • Panitumumab
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • ras Proteins / genetics

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • KRAS protein, human
  • MIrn181 microRNA, human
  • MicroRNAs
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Panitumumab
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Cetuximab