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Oncotarget. 2015 Nov 17;6(36):38695-704. doi: 10.18632/oncotarget.5735.

MicroRNA expression profiling identifies miR-31-5p/3p as associated with time to progression in wild-type RAS metastatic colorectal cancer treated with cetuximab.

Author information

1
Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
2
Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Masaryk University, Faculty of Medicine, Brno, Czech Republic.
3
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
4
Department of Oncology and Radiotherapy, Faculty Hospital Hradec Kralove, Hradec Kralove, Czech Republic.

Abstract

The aim of our study was to investigate whether microRNAs (miRNAs) could serve as predictive biomarkers to anti-EGFR therapy (cetuximab, panitumumab) in patients with RAS wild-type (wt-RAS) metastatic colorectal cancer (mCRC). Historical cohort of 93 patients with mCRC (2006-2009) was included and further divided into exploratory and validation cohorts. MiRNAs expression profiling was performed on the exploratory cohort of 41 wt-KRAS mCRC patients treated with cetuximab to identify miRNAs associated with time to progression (TTP). The validation was performed on two independent cohorts: 28 patients of wt-RAS mCRC treated with cetuximab and 24 patients of wt-RAS mCRC treated with panitumumab. We identified 9 miRNAs with significantly different expression between responders and non-responders to cetuximab therapy (P ≤ 0.01). These 9 miRNAs were further evaluated in two independent cohorts of patients and miR-31-3p (P < 0.001) and miR-31-5p (P < 0.001) were successfully confirmed as strongly associated with TTP in wt-RAS mCRC patients treated with cetuximab but not panitumumab. When evaluated on the complete cohort of cetuximab patients (N = 69), miR-31-3p (HR, 5.10; 95% CI, 2.52-10.32; P < 0.001) and miR-31-5p (HR, 4.80; 95% CI, 2.50-9.24; P < 0.001) were correlated with TTP on the comparable level of significance. There was no difference in miR-31-5p/3p expression levels in RAS mutated and wild-type tumor samples. MiR-31-5p/3p are promising predictive biomarkers of cetuximab response in wt-RAS mCRC patients.

KEYWORDS:

EGFR; cetuximab; metastatic colorectal cancer; microRNA; panitumumab

PMID:
26497852
PMCID:
PMC4770730
DOI:
10.18632/oncotarget.5735
[Indexed for MEDLINE]
Free PMC Article

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