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MicroRNA expression profiling identifies miR-31-5p/3p as associated with time to progression in wild-type RAS metastatic colorectal cancer treated with cetuximab
J. Mlcochova, P. Faltejskova-Vychytilova, M. Ferracin, B. Zagatti, L. Radova, M. Svoboda, R. Nemecek, S. John, I. Kiss, R. Vyzula, M. Negrini, O. Slaby,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
        Grantová podpora
          
              NT13860 
          
      MZ0   
          
            CEP - Centrální evidence projektů  
          
      
      
  Digitální knihovna  NLK 
   
   
      Plný text - Článek
   
   
   
   
      Zdroj
   
   
 NLK 
   
      Free Medical Journals
   
    od 2010
   
      Freely Accessible Journals
   
    od 2010
   
      PubMed Central
   
    od 2010
   
      Europe PubMed Central
   
    od 2010
   
      Open Access Digital Library
   
    od 2010-01-01
    
    PubMed
          
           26497852
           
          
          
    DOI
          
           10.18632/oncotarget.5735
           
          
          
  
    Knihovny.cz E-zdroje
    
  
              
      
- MeSH
- buňky HT-29 MeSH
- cetuximab terapeutické užití MeSH
- dospělí MeSH
- erbB receptory antagonisté a inhibitory MeSH
- HCT116 buňky MeSH
- kohortové studie MeSH
- kolorektální nádory farmakoterapie genetika metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA biosyntéza genetika MeSH
- monoklonální protilátky terapeutické užití MeSH
- protinádorové látky aplikace a dávkování terapeutické užití MeSH
- ras proteiny genetika MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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
Citace poskytuje Crossref.org
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