Portrait of DNA methylated genes predictive of poor prognosis in head and neck cancer and the implication for targeted therapy

Abstract In addition to chronic infection with human papilloma virus (HPV) and exposure to environmental carcinogens, genetic and epigenetic factors act as major risk factors for head and neck cancer (HNC) development and progression. Here, we conducted a systematic review in order to assess whether...

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Autores principales:	Jessica Hier, Olivia Vachon, Allison Bernstein, Iman Ibrahim, Alex Mlynarek, Michael Hier, Moulay A. Alaoui-Jamali, Mariana Maschietto, Sabrina Daniela da Silva
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/752971cae6224eb0966ca47035866401
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spelling	oai:doaj.org-article:752971cae6224eb0966ca470358664012021-12-02T17:02:05ZPortrait of DNA methylated genes predictive of poor prognosis in head and neck cancer and the implication for targeted therapy10.1038/s41598-021-89476-x2045-2322https://doaj.org/article/752971cae6224eb0966ca470358664012021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89476-xhttps://doaj.org/toc/2045-2322Abstract In addition to chronic infection with human papilloma virus (HPV) and exposure to environmental carcinogens, genetic and epigenetic factors act as major risk factors for head and neck cancer (HNC) development and progression. Here, we conducted a systematic review in order to assess whether DNA hypermethylated genes are predictive of high risk of developing HNC and/or impact on survival and outcomes in non-HPV/non-tobacco/non-alcohol associated HNC. We identified 85 studies covering 32,187 subjects where the relationship between DNA methylation, risk factors and survival outcomes were addressed. Changes in DNA hypermethylation were identified for 120 genes. Interactome analysis revealed enrichment in complex regulatory pathways that coordinate cell cycle progression (CCNA1, SFN, ATM, GADD45A, CDK2NA, TP53, RB1 and RASSF1). However, not all these genes showed significant statistical association with alcohol consumption, tobacco and/or HPV infection in the multivariate analysis. Genes with the most robust HNC risk association included TIMP3, DCC, DAPK, CDH1, CCNA1, MGMT, P16, MINT31, CD44, RARβ. From these candidates, we further validated CD44 at translational level in an independent cohort of 100 patients with tongue cancer followed-up beyond 10 years. CD44 expression was associated with high-risk of tumor recurrence and metastasis (P = 0.01) in HPV-cases. In summary, genes regulated by methylation play a modulatory function in HNC susceptibility and it represent a critical therapeutic target to manage patients with advanced disease.Jessica HierOlivia VachonAllison BernsteinIman IbrahimAlex MlynarekMichael HierMoulay A. Alaoui-JamaliMariana MaschiettoSabrina Daniela da SilvaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jessica Hier Olivia Vachon Allison Bernstein Iman Ibrahim Alex Mlynarek Michael Hier Moulay A. Alaoui-Jamali Mariana Maschietto Sabrina Daniela da Silva Portrait of DNA methylated genes predictive of poor prognosis in head and neck cancer and the implication for targeted therapy
description	Abstract In addition to chronic infection with human papilloma virus (HPV) and exposure to environmental carcinogens, genetic and epigenetic factors act as major risk factors for head and neck cancer (HNC) development and progression. Here, we conducted a systematic review in order to assess whether DNA hypermethylated genes are predictive of high risk of developing HNC and/or impact on survival and outcomes in non-HPV/non-tobacco/non-alcohol associated HNC. We identified 85 studies covering 32,187 subjects where the relationship between DNA methylation, risk factors and survival outcomes were addressed. Changes in DNA hypermethylation were identified for 120 genes. Interactome analysis revealed enrichment in complex regulatory pathways that coordinate cell cycle progression (CCNA1, SFN, ATM, GADD45A, CDK2NA, TP53, RB1 and RASSF1). However, not all these genes showed significant statistical association with alcohol consumption, tobacco and/or HPV infection in the multivariate analysis. Genes with the most robust HNC risk association included TIMP3, DCC, DAPK, CDH1, CCNA1, MGMT, P16, MINT31, CD44, RARβ. From these candidates, we further validated CD44 at translational level in an independent cohort of 100 patients with tongue cancer followed-up beyond 10 years. CD44 expression was associated with high-risk of tumor recurrence and metastasis (P = 0.01) in HPV-cases. In summary, genes regulated by methylation play a modulatory function in HNC susceptibility and it represent a critical therapeutic target to manage patients with advanced disease.
format	article
author	Jessica Hier Olivia Vachon Allison Bernstein Iman Ibrahim Alex Mlynarek Michael Hier Moulay A. Alaoui-Jamali Mariana Maschietto Sabrina Daniela da Silva
author_facet	Jessica Hier Olivia Vachon Allison Bernstein Iman Ibrahim Alex Mlynarek Michael Hier Moulay A. Alaoui-Jamali Mariana Maschietto Sabrina Daniela da Silva
author_sort	Jessica Hier
title	Portrait of DNA methylated genes predictive of poor prognosis in head and neck cancer and the implication for targeted therapy
title_short	Portrait of DNA methylated genes predictive of poor prognosis in head and neck cancer and the implication for targeted therapy
title_full	Portrait of DNA methylated genes predictive of poor prognosis in head and neck cancer and the implication for targeted therapy
title_fullStr	Portrait of DNA methylated genes predictive of poor prognosis in head and neck cancer and the implication for targeted therapy
title_full_unstemmed	Portrait of DNA methylated genes predictive of poor prognosis in head and neck cancer and the implication for targeted therapy
title_sort	portrait of dna methylated genes predictive of poor prognosis in head and neck cancer and the implication for targeted therapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/752971cae6224eb0966ca47035866401
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Portrait of DNA methylated genes predictive of poor prognosis in head and neck cancer and the implication for targeted therapy

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