ArticleOncotarget2016
eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- The Influence of CYP2B6, GSTP1, and SLCO1B1 Star Allele-Predicted Phenotypes and CBR1 Genetic Variants on Effectiveness Outcomes in Patients With Hepatocellular Carcinoma Receiving Doxorubicin via Transarterial Chemoembolization.Pharmacology research & perspectives · 2025Observational
- Genetic Biomarkers of Sorafenib Response in Patients with Hepatocellular Carcinoma.International journal of molecular sciences · 2024Article
- Analysis of prognostic germline polymorphisms in patients with advanced hepatocellular carcinoma.Translational gastroenterology and hepatology · 2023Article
- Polymorphism AGT2 (rs4762) is involved in the development of dermatologic events: Proof-of-concept in hepatocellular carcinoma patients treated with sorafenib.World journal of hepatology · 2022Article
- Genetic Heterogeneity, Therapeutic Hurdle Confronting Sorafenib and Immune Checkpoint Inhibitors in Hepatocellular Carcinoma.Cancers · 2021Review
- Influence of NOS3 rs2070744 genotypes on hepatocellular carcinoma patients treated with lenvatinib.Scientific reports · 2020Article
- Is the era of sorafenib over? A review of the literature.Therapeutic advances in medical oncology · 2020Review
- Immune Checkpoint Inhibitors in the Treatment of HCC.Frontiers in oncology · 2020Review
- The role of PNI to predict survival in advanced hepatocellular carcinoma treated with Sorafenib.PloS one · 2020Article
- Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib.Medicina (Kaunas, Lithuania) · 2019Review
- Impact of Baseline Characteristics on the Overall Survival of HCC Patients Treated with Sorafenib: Ten Years of Experience.Gastrointestinal tumors · 2019Article
- Pharmacogenetics of the systemic treatment in advanced hepatocellular carcinoma.World journal of gastroenterology · 2019Review
- Article
- Involvement of endothelial nitric oxide synthase gene variants in the aggressiveness of uterine cervical cancer.Journal of Cancer · 2019Article
- Ten years of sorafenib in hepatocellular carcinoma: Are there any predictive and/or prognostic markers?World journal of gastroenterology · 2018Review
- Association of endothelial nitric oxide synthase (Journal of Cancer · 2018Article
- Antiangiogenic agents after first line and sorafenib plus chemoembolization: a systematic review.Oncotarget · 2017Review
- Immune inflammation indicators and implication for immune modulation strategies in advanced hepatocellular carcinoma patients receiving sorafenib.Oncotarget · 2016Article
- Article
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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