Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors
Autor(a) principal: | |
---|---|
Data de Publicação: | 2009 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , |
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. |
id |
UNSP_814d14e4fefc83ac26d7b984d252cb8b |
---|---|
oai_identifier_str |
oai:repositorio.unesp.br:11449/21494 |
network_acronym_str |
UNSP |
network_name_str |
Repositório Institucional da UNESP |
repository_id_str |
2946 |
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) |
repository.mail.fl_str_mv |
|
_version_ |
1808128248373051392 |