MicroRNA expression profiling identifies miR-31-5p/3p as associated with time to progression in wild-type RAS metastatic colorectal cancer treated with cetuximab
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26497852
PubMed Central
PMC4770730
DOI
10.18632/oncotarget.5735
PII: 5735
Knihovny.cz E-resources
- Keywords
- EGFR, cetuximab, metastatic colorectal cancer, microRNA, panitumumab,
- MeSH
- HT29 Cells MeSH
- Cetuximab therapeutic use MeSH
- Adult MeSH
- ErbB Receptors antagonists & inhibitors MeSH
- HCT116 Cells MeSH
- Cohort Studies MeSH
- Colorectal Neoplasms drug therapy genetics metabolism pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs biosynthesis genetics MeSH
- Antibodies, Monoclonal therapeutic use MeSH
- Panitumumab MeSH
- Antineoplastic Agents administration & dosage therapeutic use MeSH
- ras Proteins genetics MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cetuximab MeSH
- EGFR protein, human MeSH Browser
- ErbB Receptors MeSH
- MicroRNAs MeSH
- MIRN31 microRNA, human MeSH Browser
- Antibodies, Monoclonal MeSH
- Panitumumab MeSH
- Antineoplastic Agents MeSH
- ras Proteins MeSH
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
Department of Morphology Surgery and Experimental Medicine University of Ferrara Ferrara Italy
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