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	ZVV_2015_205_1314693_MicroRNA_expression_01.pdf
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.
Related projects:	CEITEC - Central European Institute of Technology