MicroRNA expression profiling identifies miR-31-5p/3p as associated with time to progression in wild-type RAS metastatic colorectal cancer treated with cetuximab
| Autor: | Manuela Ferracin, Jitka Mlčochová, Stanislav John, Barbara Zagatti, Igor Kiss, Petra Faltejskova-Vychytilova, Massimo Negrini, Ondrej Slaby, Marek Svoboda, Radim Nemecek, Rostislav Vyzula, Lenka Radová |
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| Přispěvatelé: | Mlcochova, Jitka, Faltejskova-Vychytilova, Petra, Ferracin, Manuela, Zagatti, Barbara, Radova, Lenka, Svoboda, Marek, Nemecek, Radim, John, Stanislav, Kiss, Igor, Vyzula, Rostislav, Negrini, Massimo, Slaby, Ondrej |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Oncology
Male Colorectal cancer medicine.medical_treatment Cetuximab Cohort Studies 0302 clinical medicine 0303 health sciences microRNA metastatic colorectal cancer Panitumumab Antibodies Monoclonal Middle Aged 3. Good health mir-31 ErbB Receptors 030220 oncology & carcinogenesis Cohort Female Colorectal Neoplasms HT29 Cells medicine.drug Cohort study Research Paper Adult medicine.medical_specialty EGFR Socio-culturale Antineoplastic Agents 03 medical and health sciences Internal medicine medicine Humans neoplasms 030304 developmental biology Aged business.industry Cancer medicine.disease HCT116 Cells digestive system diseases Radiation therapy MicroRNAs Immunology ras Proteins Metastatic colorectal cancer business |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Jitka Mlcochova 1 , Petra Faltejskova-Vychytilova 1, 2 , Manuela Ferracin 3 , Barbara Zagatti 3 , Lenka Radova 1 , Marek Svoboda 2 , Radim Nemecek 2 , Stanislav John 4 , Igor Kiss 2 , Rostislav Vyzula 2 , Massimo Negrini 3 , Ondrej Slaby 1, 2 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 Correspondence to: Ondrej Slaby, e-mail: on.slaby@gmail.com Massimo Negrini, e-mail: ngm@unife.it Keywords: microRNA, metastatic colorectal cancer, EGFR, cetuximab, panitumumab Received: May 17, 2015 Accepted: October 08, 2015 Published: October 20, 2015 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. |
| Databáze: | OpenAIRE |
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