Publication details

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

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Authors

MLČOCHOVÁ Jitka VYCHYTILOVÁ Petra FERRACIN Manuela ZAGATTI Barbara RADOVÁ Lenka SVOBODA Marek NĚMEČEK Radim JOHN Stanislav KISS Igor VYZULA Rostislav NEGRINI Massimo SLABÝ Ondřej

Year of publication 2015
Type Article in Periodical
Magazine / Source Oncotarget
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=5735&pubmed-linkout=1
Doi http://dx.doi.org/10.18632/oncotarget.5735
Field Oncology and hematology
Keywords microRNA; colorectal cancer; cetuximab; miR-31; progression
Attached files
Description 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 patiens 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 sucessfully 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.
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