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Genes Located on 18q23 Are Epigenetic Markers and Have Prognostic Significance for Patients with Head and Neck Cancer

Loss of heterozygosity (LOH) on chromosome 18q23 is associated with significantly decreased survival in head and neck cancer. In agreement with such tumor suppressive roles, the loss of function of genes located in this region can be achieved through LOH and promotor hypermethylation. In this study,...

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Autores principales: Misawa, Kiyoshi, Kanazawa, Takeharu, Mochizuki, Daiki, Imai, Atsushi, Mima, Masato, Yamada, Satoshi, Morita, Kotaro, Misawa, Yuki, Shinmura, Kazuya, Mineta, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468360/
https://www.ncbi.nlm.nih.gov/pubmed/30901947
http://dx.doi.org/10.3390/cancers11030401
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author Misawa, Kiyoshi
Kanazawa, Takeharu
Mochizuki, Daiki
Imai, Atsushi
Mima, Masato
Yamada, Satoshi
Morita, Kotaro
Misawa, Yuki
Shinmura, Kazuya
Mineta, Hiroyuki
author_facet Misawa, Kiyoshi
Kanazawa, Takeharu
Mochizuki, Daiki
Imai, Atsushi
Mima, Masato
Yamada, Satoshi
Morita, Kotaro
Misawa, Yuki
Shinmura, Kazuya
Mineta, Hiroyuki
author_sort Misawa, Kiyoshi
collection PubMed
description Loss of heterozygosity (LOH) on chromosome 18q23 is associated with significantly decreased survival in head and neck cancer. In agreement with such tumor suppressive roles, the loss of function of genes located in this region can be achieved through LOH and promotor hypermethylation. In this study, the methylation status of promoters of 18q23 genes in 243 head and neck cancer patients was assessed by quantitative methylation-specific PCR. Promoter methylation was then compared to various clinical characteristics and patient survival. GALR1 and SALL3 promoter methylation correlated with reduced disease-free survival (log-rank test, p = 0.018 and p = 0.013, respectively). Furthermore, based on multivariate Cox proportional hazards analysis, these methylation events were associated with poor disease-free survival, with hazard ratios of 1.600 (95% confidence interval: CI, 1.027–2.493; p = 0.038) and 1.911 (95% CI, 1.155–3.162; p = 0.012), respectively. By comparison, GALR1 and SALL3 methylation were not prognostic for overall survival in The Cancer Genome Atlas (TCGA) cohort. Our findings suggest that the methylation status of 18q23 genes could serve as important biomarkers for the prediction of clinical outcomes in well-annotated head and neck squamous cell carcinoma cohorts. GALR1 and SALL3 methylation could thus help to facilitate risk stratification for individualized treatment.
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spelling pubmed-64683602019-04-24 Genes Located on 18q23 Are Epigenetic Markers and Have Prognostic Significance for Patients with Head and Neck Cancer Misawa, Kiyoshi Kanazawa, Takeharu Mochizuki, Daiki Imai, Atsushi Mima, Masato Yamada, Satoshi Morita, Kotaro Misawa, Yuki Shinmura, Kazuya Mineta, Hiroyuki Cancers (Basel) Article Loss of heterozygosity (LOH) on chromosome 18q23 is associated with significantly decreased survival in head and neck cancer. In agreement with such tumor suppressive roles, the loss of function of genes located in this region can be achieved through LOH and promotor hypermethylation. In this study, the methylation status of promoters of 18q23 genes in 243 head and neck cancer patients was assessed by quantitative methylation-specific PCR. Promoter methylation was then compared to various clinical characteristics and patient survival. GALR1 and SALL3 promoter methylation correlated with reduced disease-free survival (log-rank test, p = 0.018 and p = 0.013, respectively). Furthermore, based on multivariate Cox proportional hazards analysis, these methylation events were associated with poor disease-free survival, with hazard ratios of 1.600 (95% confidence interval: CI, 1.027–2.493; p = 0.038) and 1.911 (95% CI, 1.155–3.162; p = 0.012), respectively. By comparison, GALR1 and SALL3 methylation were not prognostic for overall survival in The Cancer Genome Atlas (TCGA) cohort. Our findings suggest that the methylation status of 18q23 genes could serve as important biomarkers for the prediction of clinical outcomes in well-annotated head and neck squamous cell carcinoma cohorts. GALR1 and SALL3 methylation could thus help to facilitate risk stratification for individualized treatment. MDPI 2019-03-21 /pmc/articles/PMC6468360/ /pubmed/30901947 http://dx.doi.org/10.3390/cancers11030401 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Misawa, Kiyoshi
Kanazawa, Takeharu
Mochizuki, Daiki
Imai, Atsushi
Mima, Masato
Yamada, Satoshi
Morita, Kotaro
Misawa, Yuki
Shinmura, Kazuya
Mineta, Hiroyuki
Genes Located on 18q23 Are Epigenetic Markers and Have Prognostic Significance for Patients with Head and Neck Cancer
title Genes Located on 18q23 Are Epigenetic Markers and Have Prognostic Significance for Patients with Head and Neck Cancer
title_full Genes Located on 18q23 Are Epigenetic Markers and Have Prognostic Significance for Patients with Head and Neck Cancer
title_fullStr Genes Located on 18q23 Are Epigenetic Markers and Have Prognostic Significance for Patients with Head and Neck Cancer
title_full_unstemmed Genes Located on 18q23 Are Epigenetic Markers and Have Prognostic Significance for Patients with Head and Neck Cancer
title_short Genes Located on 18q23 Are Epigenetic Markers and Have Prognostic Significance for Patients with Head and Neck Cancer
title_sort genes located on 18q23 are epigenetic markers and have prognostic significance for patients with head and neck cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468360/
https://www.ncbi.nlm.nih.gov/pubmed/30901947
http://dx.doi.org/10.3390/cancers11030401
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