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A let-7 microRNA polymorphism in the KRAS 3'-UTR is prognostic in oropharyngeal cancer.
De Ruyck, Kim; Duprez, Fréderic; Ferdinande, Liesbeth; Mbah, Chamberlain; Rios-Velazquez, Emmanuel; Hoebers, Frank; Praet, Marleen; Deron, Philippe; Bonte, Katrien; Speel, Ernst-Jan; Libbrecht, Louis; De Neve, Wilfried; Lambin, Philippe; Thierens, Hubert.
Afiliação
  • De Ruyck K; Department of Basic Medical Sciences, Ghent University, Proeftuinstraat 86, B-9000 Gent, Belgium. Electronic address: kim.deruyck@UGent.be.
  • Duprez F; Department of Radiotherapy, Ghent University Hospital, De Pintelaan 185, B-9000 Gent, Belgium.
  • Ferdinande L; Department of Pathology, Ghent University Hospital, De Pintelaan 185, B-9000 Gent, Belgium.
  • Mbah C; Department of Basic Medical Sciences, Ghent University, Proeftuinstraat 86, B-9000 Gent, Belgium.
  • Rios-Velazquez E; Department of Radiation Oncology (MAASTRO Clinic), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Doctor Tanslaan 12, 6229 ET Maastricht, The Netherlands.
  • Hoebers F; Department of Radiation Oncology (MAASTRO Clinic), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Doctor Tanslaan 12, 6229 ET Maastricht, The Netherlands.
  • Praet M; Department of Pathology, Ghent University Hospital, De Pintelaan 185, B-9000 Gent, Belgium.
  • Deron P; Department of Head and Neck Surgery, Ghent University Hospital, De Pintelaan 185, B-9000 Gent, Belgium.
  • Bonte K; Department of Head and Neck Surgery, Ghent University Hospital, De Pintelaan 185, B-9000 Gent, Belgium.
  • Speel EJ; Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Doctor Tanslaan 12, 6229 ET Maastricht, The Netherlands.
  • Libbrecht L; Department of Pathology, Ghent University Hospital, De Pintelaan 185, B-9000 Gent, Belgium.
  • De Neve W; Department of Radiotherapy, Ghent University Hospital, De Pintelaan 185, B-9000 Gent, Belgium.
  • Lambin P; Department of Radiation Oncology (MAASTRO Clinic), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Doctor Tanslaan 12, 6229 ET Maastricht, The Netherlands.
  • Thierens H; Department of Basic Medical Sciences, Ghent University, Proeftuinstraat 86, B-9000 Gent, Belgium.
Cancer Epidemiol ; 38(5): 591-8, 2014 Oct.
Article em En | MEDLINE | ID: mdl-25127693
INTRODUCTION: This study aimed to investigate the effect of genetic polymorphisms in miRNA sequences, miRNA target genes and miRNA processing genes as additional biomarkers to HPV for prognosis in oropharyngeal squamous cell carcinoma (OPSCC) patients. Secondarily, the prevalence of HPV-associated OPSCC in a European cohort was mapped. METHODS: OPSCC patients (n=122) were genotyped for ten genetic polymorphisms in pre-miRNAs (pre-mir-146a, pre-mir-196a2), in miRNA biosynthesis genes (Drosha, XPO5) and in miRNA target genes (KRAS, SMC1B). HPV status was assessed by p16 immunohistochemistry (IHC) and high-risk HPV in situ hybridization (ISH) or by p16 IHC and PCR followed by enzyme-immunoassay (EIA). Overall and disease specific survival were analysed using Kaplan-Meier plots (log-rank test). Cox proportional hazard model was used to calculate hazard ratios (HR). RESULTS: The overall HPV prevalence rate in our Belgian/Dutch cohort was 27.9%. Patients with HPV(+) tumours had a better 5-years overall survival (78% vs. 46%, p=0.001) and a better 5-years disease specific survival (90% vs. 70%, p=0.016) compared to patients with HPV(-) tumours. In multivariate Cox analysis including clinical, treatment and genetic parameters, HPV negativity (HR=3.89, p=0.005), advanced T-stage (HR=1.81, p=0.050), advanced N-stage (HR=5.86, p=0.001) and >10 pack-years of smoking (HR=3.45, p=0.012) were significantly associated with reduced overall survival. The variant G-allele of the KRAS-LCS6 polymorphism was significantly associated with a better overall survival (HR=0.40, p=0.031). CONCLUSIONS: Our results demonstrate that OPSCC patients with the KRAS-LCS6 variant have a better outcome and suggest that this variant may be used as a prognostic biomarker for OPSCC.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma de Células Escamosas / Neoplasias Orofaríngeas / Proteínas Proto-Oncogênicas / Proteínas ras / MicroRNAs Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma de Células Escamosas / Neoplasias Orofaríngeas / Proteínas Proto-Oncogênicas / Proteínas ras / MicroRNAs Idioma: En Ano de publicação: 2014 Tipo de documento: Article