TY - JOUR
T1 - A let-7 microRNA polymorphism in the KRAS 3'-UTR is prognostic in oropharyngeal cancer
AU - De Ruyck, Kim
AU - Duprez, Fréderic
AU - Ferdinande, Liesbeth
AU - Mbah, Chamberlain
AU - Rios-Velazquez, Emmanuel
AU - Hoebers, Frank
AU - Praet, Marleen
AU - Deron, Philippe
AU - Bonte, Katrien
AU - Speel, Ernst-Jan
AU - Libbrecht, Louis
AU - De Neve, Wilfried
AU - Lambin, Philippe
AU - Thierens, Hubert
N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.
PY - 2014/10
Y1 - 2014/10
N2 - 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.
AB - 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.
KW - 3' Untranslated Regions
KW - Adult
KW - Aged
KW - Carcinoma, Squamous Cell
KW - Female
KW - Follow-Up Studies
KW - Genotype
KW - Humans
KW - Kaplan-Meier Estimate
KW - Male
KW - MicroRNAs
KW - Middle Aged
KW - Oropharyngeal Neoplasms
KW - Papillomavirus Infections
KW - Polymorphism, Genetic
KW - Prevalence
KW - Prognosis
KW - Proportional Hazards Models
KW - Proto-Oncogene Proteins
KW - Survival Rate
KW - ras Proteins
U2 - 10.1016/j.canep.2014.07.008
DO - 10.1016/j.canep.2014.07.008
M3 - Article
C2 - 25127693
SN - 1877-7821
VL - 38
SP - 591
EP - 598
JO - Cancer Epidemiology
JF - Cancer Epidemiology
IS - 5
ER -