Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors

Detalhes bibliográficos
Autor(a) principal: Calmon, Marilia de Freitas [UNESP]
Data de Publicação: 2009
Outros Autores: Rodrigues, Rodrigo V., Kaneto, Carla M., Moura, Ricardo P., Silva, Sabrina D., Mota, Louise Danielle C., Pinheiro, Daniel G., Torres, Cesar, de Carvalho, Alex F., Cury, Patricia M., Nunes, Fabio D., Nishimoto, Ines Nobuko, Soares, Fernando A., da Silva, Adriana M. A., Kowalski, Luis P., Brentani, Helena, Zanelli, Cleslei Fernando [UNESP], Silva, Wilson A., Rahal, Paula [UNESP], Tajara, Eloiza H., Carraro, Dirce M., Camargo, Anamaria A., Valentini, Sandro Roberto [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://www.neoplasia.com/abstract.php?msid=2814
http://hdl.handle.net/11449/21494
Resumo: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease affecting the epithelium of the oral cavity, pharynx and larynx. Conditions of most patients are diagnosed at late stages of the disease, and no sensitive and specific predictors of aggressive behavior have been identified yet. Therefore, early detection and prognostic biomarkers are highly desirable for a more rational management of the disease. Hypermethylation of CpG islands is one of the most important epigenetic mechanisms that leads to gene silencing in tumors and has been extensively used for the identification of biomarkers. In this study, we combined rapid subtractive hybridization and microarray analysis in a hierarchical manner to select genes that are putatively reactivated by the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) in HNSCC cell lines (FaDu, UM-SCC-14A, UM-SCC-17A, UM-SCC-38A). This combined analysis identified 78 genes, 35 of which were reactivated in at least 2 cell lines and harbored a CpG island at their 5' region. Reactivation of 3 of these 35 genes (CRABP2, MX1, and SLC15A3) was confirmed by quantitative real-time polymerase chain reaction (PCR; fold change, >= 3). Bisulfite sequencing of their CpG islands revealed that they are indeed differentially methylated in the HNSCC cell lines. Using methylation-specific PCR, we detected a higher frequency of CRABP2 (58.1% for region 1) and MX1 (46.3%) hypermethylation in primary HNSCC when compared with lymphocytes from healthy individuals. Finally, absence of the CRABP2 protein was associated with decreased disease-free survival rates, supporting a potential use of CRABP2 expression as a prognostic biomarker for HNSCC patients.
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spelling Epigenetic Silencing of CRABP2 and MX1 in Head and Neck TumorsHead and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease affecting the epithelium of the oral cavity, pharynx and larynx. Conditions of most patients are diagnosed at late stages of the disease, and no sensitive and specific predictors of aggressive behavior have been identified yet. Therefore, early detection and prognostic biomarkers are highly desirable for a more rational management of the disease. Hypermethylation of CpG islands is one of the most important epigenetic mechanisms that leads to gene silencing in tumors and has been extensively used for the identification of biomarkers. In this study, we combined rapid subtractive hybridization and microarray analysis in a hierarchical manner to select genes that are putatively reactivated by the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) in HNSCC cell lines (FaDu, UM-SCC-14A, UM-SCC-17A, UM-SCC-38A). This combined analysis identified 78 genes, 35 of which were reactivated in at least 2 cell lines and harbored a CpG island at their 5' region. Reactivation of 3 of these 35 genes (CRABP2, MX1, and SLC15A3) was confirmed by quantitative real-time polymerase chain reaction (PCR; fold change, >= 3). Bisulfite sequencing of their CpG islands revealed that they are indeed differentially methylated in the HNSCC cell lines. Using methylation-specific PCR, we detected a higher frequency of CRABP2 (58.1% for region 1) and MX1 (46.3%) hypermethylation in primary HNSCC when compared with lymphocytes from healthy individuals. Finally, absence of the CRABP2 protein was associated with decreased disease-free survival rates, supporting a potential use of CRABP2 expression as a prognostic biomarker for HNSCC patients.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)UNESP, Fac Ciencias Farmaceut, Sch Pharmaceut Sci, Dept Biol Sci, BR-14801902 Araraquara, SP, BrazilHeliopolis Hosp, BR-04231030 São Paulo, BrazilUniv São Paulo, Sch Dent, BR-05508000 São Paulo, BrazilAC Camargo Canc Hosp, Med & Res Ctr, BR-01509900 São Paulo, BrazilOswaldo Cruz Hosp, Ludwig Inst Canc Res, BR-01323903 São Paulo, BrazilUSP, Sch Med, Dept Genet, BR-14051140 Ribeirao Preto, SP, BrazilUniv São Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, BR-05508090 São Paulo, BrazilFAMERP, Sch Med, Dept Biol Mol, BR-15090000 Sao Jose do Rio Preto, SP, BrazilUNESP, IBILCE, Dept Biol, BR-15091450 Sao Jose do Rio Preto, SP, BrazilUNESP, Fac Ciencias Farmaceut, Sch Pharmaceut Sci, Dept Biol Sci, BR-14801902 Araraquara, SP, BrazilUNESP, IBILCE, Dept Biol, BR-15091450 Sao Jose do Rio Preto, SP, BrazilNeoplasia PressUniversidade Estadual Paulista (Unesp)Heliopolis HospAC Camargo Canc HospOswaldo Cruz HospUniversidade de São Paulo (USP)Faculdade de Medicina de São José do Rio Preto (FAMERP)Calmon, Marilia de Freitas [UNESP]Rodrigues, Rodrigo V.Kaneto, Carla M.Moura, Ricardo P.Silva, Sabrina D.Mota, Louise Danielle C.Pinheiro, Daniel G.Torres, Cesarde Carvalho, Alex F.Cury, Patricia M.Nunes, Fabio D.Nishimoto, Ines NobukoSoares, Fernando A.da Silva, Adriana M. A.Kowalski, Luis P.Brentani, HelenaZanelli, Cleslei Fernando [UNESP]Silva, Wilson A.Rahal, Paula [UNESP]Tajara, Eloiza H.Carraro, Dirce M.Camargo, Anamaria A.Valentini, Sandro Roberto [UNESP]2014-05-20T14:00:51Z2014-05-20T14:00:51Z2009-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1329-U100http://www.neoplasia.com/abstract.php?msid=2814Neoplasia. Ann Arbor: Neoplasia Press, v. 11, n. 12, p. 1329-U100, 2009.1522-8002http://hdl.handle.net/11449/2149410.1593/neo.91110WOS:0002724740000097991082362671212916560146943624015256654089001950000-0001-5693-61480000-0001-7831-1149Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengNeoplasia2,133info:eu-repo/semantics/openAccess2024-06-24T13:06:42Zoai:repositorio.unesp.br:11449/21494Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T13:34:06.641420Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors
title Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors
spellingShingle Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors
Calmon, Marilia de Freitas [UNESP]
title_short Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors
title_full Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors
title_fullStr Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors
title_full_unstemmed Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors
title_sort Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors
author Calmon, Marilia de Freitas [UNESP]
author_facet Calmon, Marilia de Freitas [UNESP]
Rodrigues, Rodrigo V.
Kaneto, Carla M.
Moura, Ricardo P.
Silva, Sabrina D.
Mota, Louise Danielle C.
Pinheiro, Daniel G.
Torres, Cesar
de Carvalho, Alex F.
Cury, Patricia M.
Nunes, Fabio D.
Nishimoto, Ines Nobuko
Soares, Fernando A.
da Silva, Adriana M. A.
Kowalski, Luis P.
Brentani, Helena
Zanelli, Cleslei Fernando [UNESP]
Silva, Wilson A.
Rahal, Paula [UNESP]
Tajara, Eloiza H.
Carraro, Dirce M.
Camargo, Anamaria A.
Valentini, Sandro Roberto [UNESP]
author_role author
author2 Rodrigues, Rodrigo V.
Kaneto, Carla M.
Moura, Ricardo P.
Silva, Sabrina D.
Mota, Louise Danielle C.
Pinheiro, Daniel G.
Torres, Cesar
de Carvalho, Alex F.
Cury, Patricia M.
Nunes, Fabio D.
Nishimoto, Ines Nobuko
Soares, Fernando A.
da Silva, Adriana M. A.
Kowalski, Luis P.
Brentani, Helena
Zanelli, Cleslei Fernando [UNESP]
Silva, Wilson A.
Rahal, Paula [UNESP]
Tajara, Eloiza H.
Carraro, Dirce M.
Camargo, Anamaria A.
Valentini, Sandro Roberto [UNESP]
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Heliopolis Hosp
AC Camargo Canc Hosp
Oswaldo Cruz Hosp
Universidade de São Paulo (USP)
Faculdade de Medicina de São José do Rio Preto (FAMERP)
dc.contributor.author.fl_str_mv Calmon, Marilia de Freitas [UNESP]
Rodrigues, Rodrigo V.
Kaneto, Carla M.
Moura, Ricardo P.
Silva, Sabrina D.
Mota, Louise Danielle C.
Pinheiro, Daniel G.
Torres, Cesar
de Carvalho, Alex F.
Cury, Patricia M.
Nunes, Fabio D.
Nishimoto, Ines Nobuko
Soares, Fernando A.
da Silva, Adriana M. A.
Kowalski, Luis P.
Brentani, Helena
Zanelli, Cleslei Fernando [UNESP]
Silva, Wilson A.
Rahal, Paula [UNESP]
Tajara, Eloiza H.
Carraro, Dirce M.
Camargo, Anamaria A.
Valentini, Sandro Roberto [UNESP]
description Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease affecting the epithelium of the oral cavity, pharynx and larynx. Conditions of most patients are diagnosed at late stages of the disease, and no sensitive and specific predictors of aggressive behavior have been identified yet. Therefore, early detection and prognostic biomarkers are highly desirable for a more rational management of the disease. Hypermethylation of CpG islands is one of the most important epigenetic mechanisms that leads to gene silencing in tumors and has been extensively used for the identification of biomarkers. In this study, we combined rapid subtractive hybridization and microarray analysis in a hierarchical manner to select genes that are putatively reactivated by the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) in HNSCC cell lines (FaDu, UM-SCC-14A, UM-SCC-17A, UM-SCC-38A). This combined analysis identified 78 genes, 35 of which were reactivated in at least 2 cell lines and harbored a CpG island at their 5' region. Reactivation of 3 of these 35 genes (CRABP2, MX1, and SLC15A3) was confirmed by quantitative real-time polymerase chain reaction (PCR; fold change, >= 3). Bisulfite sequencing of their CpG islands revealed that they are indeed differentially methylated in the HNSCC cell lines. Using methylation-specific PCR, we detected a higher frequency of CRABP2 (58.1% for region 1) and MX1 (46.3%) hypermethylation in primary HNSCC when compared with lymphocytes from healthy individuals. Finally, absence of the CRABP2 protein was associated with decreased disease-free survival rates, supporting a potential use of CRABP2 expression as a prognostic biomarker for HNSCC patients.
publishDate 2009
dc.date.none.fl_str_mv 2009-12-01
2014-05-20T14:00:51Z
2014-05-20T14:00:51Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://www.neoplasia.com/abstract.php?msid=2814
Neoplasia. Ann Arbor: Neoplasia Press, v. 11, n. 12, p. 1329-U100, 2009.
1522-8002
http://hdl.handle.net/11449/21494
10.1593/neo.91110
WOS:000272474000009
7991082362671212
9165601469436240
1525665408900195
0000-0001-5693-6148
0000-0001-7831-1149
url http://www.neoplasia.com/abstract.php?msid=2814
http://hdl.handle.net/11449/21494
identifier_str_mv Neoplasia. Ann Arbor: Neoplasia Press, v. 11, n. 12, p. 1329-U100, 2009.
1522-8002
10.1593/neo.91110
WOS:000272474000009
7991082362671212
9165601469436240
1525665408900195
0000-0001-5693-6148
0000-0001-7831-1149
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Neoplasia
2,133
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 1329-U100
dc.publisher.none.fl_str_mv Neoplasia Press
publisher.none.fl_str_mv Neoplasia Press
dc.source.none.fl_str_mv Web of Science
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
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