miR-31-3p enables clinicians to identify RAS WT mCRC patients for which first-line anti-EGFR treatment will be of greater clinical benefit versus anti-VEGF therapy or when second or further lines of treatment with anti-EGFR therapy is beneficial to patients with RAS WT mCRC.

miR-31-3p assists clinicians to identify the most appropriate therapeutic strategy for RAS wild type patients with metastatic colorectal cancer (mCRC) by measuring the expression of miR-31-3p, a microRNA biomarker which has been shown to be associated with anti-EGFR therapy response in this patient population.1-5


Results from prospective-retrospective study 

miR-31-3p expression was measured in primary tumors from 340 RAS WT patients with metastatic colorectal cancer enrolled in the FIRE-3 trial. Patients were split into low or high miR-31-3p expression subgroups according to a pre-defined cut-off.

Results from the study demonstrated that RAS WT mCRC patients with low miR-31-3p expression treated with cetuximab had a:

  •  40% risk reduction for death when treated with cetuximab compared to bevacizumab.
  •  12 month longer median overall survival when treated with cetuximab versus bevacizumab.

There was no difference in survival outcomes between cetuximab and bevacizumab in patients with high miR-31-3p expression.

The results of this study demonstrate that low miR-31-3p expression levels predicts survival benefit with cetuximab in RAS WT metastatic colorectal cancer patients receiving FOLFIRI therapy.5,6

Additional data from the study:


There was a significantly higher investigator-assessed objective response in patients with low miR-31-3p expression treated with cetuximab + FOLFIRI vs. bevacizumab + FOLFIRI.  OR = 4.49 [2.07 ; 9.76], p=0.0001

Odds ratio [95% CI] adjusted on age, number of organs and BRAF status. Excludes patients with missing data.



Depth of response (DoR) for patients treated with cetuximab + FOLFIRI was significantly correlated with miR-31-3p expression levels. 

There was no correlation observed between DoR and miR-31-3p expression in patients treated with bevacizumab + FOLFIRI.



Study conclusions:

  •  Low miR-31-3p expression favors first-line treatment with cetuximab for RAS WT mCRC patients.5,6
  •  High miR-31-3p expressors have no difference in outcomes when treated with anti-EGFR or anti-VEGF therapy.5,6


Click here to review the results of additional studies  which have demonstrated the predictive effect miR-31-3p expression has on response to EGFR inhibitors in patients with mCRC.


1. Manceau G, Imbeaud S, Thiébaut R, et al. Clin Cancer Res. 2014; 20: 3338-47.
2. Mosakhani N, Lahti L, Borze I, et al. Cancer Genet. 2012; 205: 545-51.
3. Laurent-Puig P, Bridgewater JA, Primrose JN, et al. J Clin Oncol. 2015; 32: (suppl; abstr 3523).
4. Laurent-Puig P, Paget-Bailly S, Vernerey D, et al. J Clin Oncol. 2015; 33: (suppl; abstr 3547).
5. Laurent-Puig P, Grisoni ML, Heinemann V, et. al. J Clin Oncol . 2016; 34 (suppl; abstr 3516).
6. Data on file.