Cargando…

eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study

Sorafenib may reduce endothelial nitric oxide synthase (eNOS) activity by inhibiting vascular endothelial growth factor receptors (VEGF-R), leading to a decrease in nitric oxide production. In the Italian multicenter ePHAS (eNOS polymorphisms in HCC and sorafenib) study, we analyzed the role of eNOS...

Descripción completa

Detalles Bibliográficos
Autores principales: Gardini, Andrea Casadei, Marisi, Giorgia, Faloppi, Luca, Scarpi, Emanuela, Foschi, Francesco Giuseppe, Iavarone, Massimo, Lauletta, Gianfranco, Corbelli, Jody, Valgiusti, Martina, Facchetti, Floriana, Corte, Cristina della, Neri, Luca Maria, Tamberi, Stefano, Cascinu, Stefano, Scartozzi, Mario, Amadori, Dino, Nanni, Oriana, Tenti, Elena, Ulivi, Paola, Frassineti, Giovanni Luca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053704/
https://www.ncbi.nlm.nih.gov/pubmed/27058899
http://dx.doi.org/10.18632/oncotarget.8569
_version_ 1782458465995718656
author Gardini, Andrea Casadei
Marisi, Giorgia
Faloppi, Luca
Scarpi, Emanuela
Foschi, Francesco Giuseppe
Iavarone, Massimo
Lauletta, Gianfranco
Corbelli, Jody
Valgiusti, Martina
Facchetti, Floriana
Corte, Cristina della
Neri, Luca Maria
Tamberi, Stefano
Cascinu, Stefano
Scartozzi, Mario
Amadori, Dino
Nanni, Oriana
Tenti, Elena
Ulivi, Paola
Frassineti, Giovanni Luca
author_facet Gardini, Andrea Casadei
Marisi, Giorgia
Faloppi, Luca
Scarpi, Emanuela
Foschi, Francesco Giuseppe
Iavarone, Massimo
Lauletta, Gianfranco
Corbelli, Jody
Valgiusti, Martina
Facchetti, Floriana
Corte, Cristina della
Neri, Luca Maria
Tamberi, Stefano
Cascinu, Stefano
Scartozzi, Mario
Amadori, Dino
Nanni, Oriana
Tenti, Elena
Ulivi, Paola
Frassineti, Giovanni Luca
author_sort Gardini, Andrea Casadei
collection PubMed
description Sorafenib may reduce endothelial nitric oxide synthase (eNOS) activity by inhibiting vascular endothelial growth factor receptors (VEGF-R), leading to a decrease in nitric oxide production. In the Italian multicenter ePHAS (eNOS polymorphisms in HCC and sorafenib) study, we analyzed the role of eNOS polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Our retrospective study included a training cohort of 41 HCC patients and a validation cohort of 87 HCC patients, all undergoing sorafenib treatment. Three eNOS polymorphisms (eNOS -786T>C, eNOS VNTR 27bp 4a/b and eNOS+894G>T) were analyzed by direct sequencing or Real Time PCR in relation to progression-free survival (PFS) and overall survival (OS) (log-rank test). In univariate analysis, training cohort patients homozygous for eNOS haplotype (HT1:T-4b at eNOS-786/eNOS VNTR) had a lower median PFS (2.6 vs. 5.8 months, P < 0.0001) and OS (3.2 vs.14.6 months, P = 0.024) than those with other haplotypes. In the validation set, patients homozygous for HT1 had a lower median PFS (2.0 vs. 6.7 months, P < 0.0001) and OS (6.4 vs.18.0 months, P < 0.0001) than those with other haplotypes. Multivariate analysis confirmed this haplotype as the only independent prognostic factor. Our results suggest that haplotype HT1 in the eNOS gene may be capable of identifying a subset of HCC patients who are resistant to sorafenib.
format Online
Article
Text
id pubmed-5053704
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-50537042016-10-12 eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study Gardini, Andrea Casadei Marisi, Giorgia Faloppi, Luca Scarpi, Emanuela Foschi, Francesco Giuseppe Iavarone, Massimo Lauletta, Gianfranco Corbelli, Jody Valgiusti, Martina Facchetti, Floriana Corte, Cristina della Neri, Luca Maria Tamberi, Stefano Cascinu, Stefano Scartozzi, Mario Amadori, Dino Nanni, Oriana Tenti, Elena Ulivi, Paola Frassineti, Giovanni Luca Oncotarget Research Paper Sorafenib may reduce endothelial nitric oxide synthase (eNOS) activity by inhibiting vascular endothelial growth factor receptors (VEGF-R), leading to a decrease in nitric oxide production. In the Italian multicenter ePHAS (eNOS polymorphisms in HCC and sorafenib) study, we analyzed the role of eNOS polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Our retrospective study included a training cohort of 41 HCC patients and a validation cohort of 87 HCC patients, all undergoing sorafenib treatment. Three eNOS polymorphisms (eNOS -786T>C, eNOS VNTR 27bp 4a/b and eNOS+894G>T) were analyzed by direct sequencing or Real Time PCR in relation to progression-free survival (PFS) and overall survival (OS) (log-rank test). In univariate analysis, training cohort patients homozygous for eNOS haplotype (HT1:T-4b at eNOS-786/eNOS VNTR) had a lower median PFS (2.6 vs. 5.8 months, P < 0.0001) and OS (3.2 vs.14.6 months, P = 0.024) than those with other haplotypes. In the validation set, patients homozygous for HT1 had a lower median PFS (2.0 vs. 6.7 months, P < 0.0001) and OS (6.4 vs.18.0 months, P < 0.0001) than those with other haplotypes. Multivariate analysis confirmed this haplotype as the only independent prognostic factor. Our results suggest that haplotype HT1 in the eNOS gene may be capable of identifying a subset of HCC patients who are resistant to sorafenib. Impact Journals LLC 2016-04-04 /pmc/articles/PMC5053704/ /pubmed/27058899 http://dx.doi.org/10.18632/oncotarget.8569 Text en Copyright: © 2016 Gardini et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Gardini, Andrea Casadei
Marisi, Giorgia
Faloppi, Luca
Scarpi, Emanuela
Foschi, Francesco Giuseppe
Iavarone, Massimo
Lauletta, Gianfranco
Corbelli, Jody
Valgiusti, Martina
Facchetti, Floriana
Corte, Cristina della
Neri, Luca Maria
Tamberi, Stefano
Cascinu, Stefano
Scartozzi, Mario
Amadori, Dino
Nanni, Oriana
Tenti, Elena
Ulivi, Paola
Frassineti, Giovanni Luca
eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study
title eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study
title_full eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study
title_fullStr eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study
title_full_unstemmed eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study
title_short eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study
title_sort enos polymorphisms and clinical outcome in advanced hcc patients receiving sorafenib: final results of the ephas study
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053704/
https://www.ncbi.nlm.nih.gov/pubmed/27058899
http://dx.doi.org/10.18632/oncotarget.8569
work_keys_str_mv AT gardiniandreacasadei enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT marisigiorgia enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT faloppiluca enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT scarpiemanuela enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT foschifrancescogiuseppe enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT iavaronemassimo enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT laulettagianfranco enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT corbellijody enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT valgiustimartina enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT facchettifloriana enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT cortecristinadella enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT nerilucamaria enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT tamberistefano enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT cascinustefano enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT scartozzimario enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT amadoridino enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT nannioriana enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT tentielena enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT ulivipaola enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy
AT frassinetigiovanniluca enospolymorphismsandclinicaloutcomeinadvancedhccpatientsreceivingsorafenibfinalresultsoftheephasstudy