Association of MicroRNA-31-5p with Clinical Efficacy of Anti-EGFR Therapy in Patients with Metastatic Colorectal Cancer

Ann Surg Oncol. 2015 Aug;22(8):2640-8. doi: 10.1245/s10434-014-4264-7. Epub 2014 Dec 4.


Background: Gene mutations in the pathway downstream of epidermal growth factor receptor (EGFR) are considered to induce resistance to anti-EGFR therapy in colorectal cancer (CRC). We recently reported that microRNA-31 (miR-31)-5p may regulate BRAF activation and play a role in the signaling pathway downstream of EGFR in CRC. Therefore, we hypothesized that miR-31-5p can be a useful biomarker for anti-EGFR therapy in CRC.

Methods: We evaluated miR-31-5p expression and gene mutations [KRAS (codon 61 or 146), NRAS (codon 12, 13, or 61), and BRAF (V600E)] in the EGFR downstream pathway in 102 CRC patients harboring KRAS (codon 12 or 13) wild-type who were treated with anti-EGFR therapeutics. Progression-free survival (PFS) and overall survival (OS) were evaluated.

Results: KRAS (codon 61 or 146), NRAS, and BRAF mutations were detected in 6.9, 6.9, and 5.9 % patients, respectively. Compared with CRCs with at least one mutation (n = 20), significantly better PFS (P = 0.0003) but insignificantly better OS were observed in CRCs harboring all wild-type genes (KRAS, NRAS, and BRAF). High miR-31-5p expression was identified in 11 % (n = 11) patients and was significantly associated with shorter PFS (P = 0.003). In CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS (P = 0.027).

Conclusions: High miR-31-5p expression was associated with shorter PFS in patients with CRC treated with anti-EGFR therapeutics. Moreover, in CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS, suggesting that it may be a useful and additional prognostic biomarker for anti-EGFR therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Cetuximab / therapeutic use
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • DNA Mutational Analysis
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors*
  • Female
  • GTP Phosphohydrolases / genetics
  • Gene Expression
  • Humans
  • Male
  • Membrane Proteins / genetics
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Metastasis
  • Panitumumab
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Response Evaluation Criteria in Solid Tumors
  • Survival Rate


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • KRAS protein, human
  • MIRN31 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Panitumumab
  • ErbB Receptors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human
  • Proto-Oncogene Proteins p21(ras)
  • Cetuximab