MicroRNA expression profiling identifies miR-31-5p/3p as associated with time to progression in wild-type RAS metastatic colorectal cancer treated with cetuximab.
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.
Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Jitka
J
Mlcochova
Central European Institute of Technology, Masaryk University, Brno, Czech Republic.|Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Masaryk University, Faculty of Medicine, Brno, Czech Republic.
Petra
P
Faltejskova-Vychytilova
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
Manuela
M
Ferracin
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
Barbara
B
Zagatti
Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Lenka
L
Radova
Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Masaryk University, Faculty of Medicine, Brno, Czech Republic.
Marek
M
Svoboda
Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Masaryk University, Faculty of Medicine, Brno, Czech Republic.
Radim
R
Nemecek
Department of Oncology and Radiotherapy, Faculty Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
Stanislav
S
John
Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Masaryk University, Faculty of Medicine, Brno, Czech Republic.
Igor
I
Kiss
Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Masaryk University, Faculty of Medicine, Brno, Czech Republic.
Rostislav
R
Vyzula
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
Massimo
M
Negrini
Central European Institute of Technology, Masaryk University, Brno, Czech Republic.|Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Masaryk University, Faculty of Medicine, Brno, Czech Republic.
Ondrej
O
Slaby
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000068818:Cetuximab / Q000627:therapeutic use*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D000077544:Panitumumab; D018631:ras Proteins / Q000235:genetics
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D018631:ras Proteins; D000068818:Cetuximab
EGFR; cetuximab; metastatic colorectal cancer; microRNA; panitumumab