Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients

Autores
Bracalente, María Candelaria; Rinflerch, Adriana Raquel; Ibañez, Irene Laura; García Chicote, Francisco Manuel; Volonteri, Victoria; Galimberti, Gastón N.; Klamt, Fabio; Duran, Hebe Alicia
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Melanoma is an aggressive cancer with highly metastatic ability. We propose cofilin-1, a key protein in the regulation of actin dynamics and migration, as a prognostic marker. We determined cofilin-1 levels in a retrospective cohort of patients with melanomas and benign lesions of melanocytes (nevi) by immunohistochemistry. Higher cofilin-1 levels were found in malignant melanoma (MM) with Breslow Index (BI)>2 vs MM with BI<2, melanoma in situ (MIS) and nevi and also in MM with metastasis vs MM without detected metastasis. Kaplan-Meier survival curves were performed, clustering patients according to either the type of melanocytic lesions or cofilin-1 level. Survival curves demonstrated worse prognosis of patients with high vs low cofilin-1 levels. TCGA database analysis of melanoma also showed low survival in patients with upregulated cofilin-1 mRNA vs patients without alteration in CFL1 mRNA expression. As cofilin-1 has a dual function depending on its intracellular localization, we evaluated nuclear and cytoplasmic levels of cofilin-1 in melanoma and nevi samples by immunofluorescence. MM with high Breslow index and metastatic cells not only presented cytoplasmic cofilin-1, but also showed this protein at the nucleus. An increase in nuclear/cytoplasmic cofilin-1 mean fluorescence ratio was observed in MM with BI>2 vs MM with BI<2, MIS and nevi. In conclusion, an association of cofilin-1 levels with malignant features and an inverse correlation with survival were demonstrated. Moreover, this study suggests that not only the higher levels of cofilin-1, but also its nuclear localization can be proposed as marker of worse outcome of patients with melanoma.
Fil: Bracalente, María Candelaria. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rinflerch, Adriana Raquel. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ibañez, Irene Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina
Fil: García Chicote, Francisco Manuel. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Volonteri, Victoria. Hospital Italiano; Argentina
Fil: Galimberti, Gastón N.. Hospital Italiano; Argentina
Fil: Klamt, Fabio. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Duran, Hebe Alicia. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
Materia
COFILIN-1
MELANOMA
METASTASIS
NUCLEAR LOCALIZATION
PROGNOSIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/102977
Acceder
id CONICETDig_fa09593cac368ef2a8aa1c60d1c84fac
oai_identifier_str oai:ri.conicet.gov.ar:11336/102977
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patientsBracalente, María CandelariaRinflerch, Adriana RaquelIbañez, Irene LauraGarcía Chicote, Francisco ManuelVolonteri, VictoriaGalimberti, Gastón N.Klamt, FabioDuran, Hebe AliciaCOFILIN-1MELANOMAMETASTASISNUCLEAR LOCALIZATIONPROGNOSIShttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Melanoma is an aggressive cancer with highly metastatic ability. We propose cofilin-1, a key protein in the regulation of actin dynamics and migration, as a prognostic marker. We determined cofilin-1 levels in a retrospective cohort of patients with melanomas and benign lesions of melanocytes (nevi) by immunohistochemistry. Higher cofilin-1 levels were found in malignant melanoma (MM) with Breslow Index (BI)>2 vs MM with BI<2, melanoma in situ (MIS) and nevi and also in MM with metastasis vs MM without detected metastasis. Kaplan-Meier survival curves were performed, clustering patients according to either the type of melanocytic lesions or cofilin-1 level. Survival curves demonstrated worse prognosis of patients with high vs low cofilin-1 levels. TCGA database analysis of melanoma also showed low survival in patients with upregulated cofilin-1 mRNA vs patients without alteration in CFL1 mRNA expression. As cofilin-1 has a dual function depending on its intracellular localization, we evaluated nuclear and cytoplasmic levels of cofilin-1 in melanoma and nevi samples by immunofluorescence. MM with high Breslow index and metastatic cells not only presented cytoplasmic cofilin-1, but also showed this protein at the nucleus. An increase in nuclear/cytoplasmic cofilin-1 mean fluorescence ratio was observed in MM with BI>2 vs MM with BI<2, MIS and nevi. In conclusion, an association of cofilin-1 levels with malignant features and an inverse correlation with survival were demonstrated. Moreover, this study suggests that not only the higher levels of cofilin-1, but also its nuclear localization can be proposed as marker of worse outcome of patients with melanoma.Fil: Bracalente, María Candelaria. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rinflerch, Adriana Raquel. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ibañez, Irene Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: García Chicote, Francisco Manuel. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Volonteri, Victoria. Hospital Italiano; ArgentinaFil: Galimberti, Gastón N.. Hospital Italiano; ArgentinaFil: Klamt, Fabio. Universidade Federal do Rio Grande do Sul; BrasilFil: Duran, Hebe Alicia. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaImpact Journals2018-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/102977Bracalente, María Candelaria; Rinflerch, Adriana Raquel; Ibañez, Irene Laura; García Chicote, Francisco Manuel; Volonteri, Victoria; et al.; Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients; Impact Journals; Oncotarget; 9; 35; 5-2018; 24097-241081949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.oncotarget.com/article/25303/info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.25303info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:31:43Zoai:ri.conicet.gov.ar:11336/102977instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:31:43.813CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients
title Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients
spellingShingle Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients
Bracalente, María Candelaria
COFILIN-1
MELANOMA
METASTASIS
NUCLEAR LOCALIZATION
PROGNOSIS
title_short Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients
title_full Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients
title_fullStr Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients
title_full_unstemmed Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients
title_sort Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients
dc.creator.none.fl_str_mv Bracalente, María Candelaria
Rinflerch, Adriana Raquel
Ibañez, Irene Laura
García Chicote, Francisco Manuel
Volonteri, Victoria
Galimberti, Gastón N.
Klamt, Fabio
Duran, Hebe Alicia
author Bracalente, María Candelaria
author_facet Bracalente, María Candelaria
Rinflerch, Adriana Raquel
Ibañez, Irene Laura
García Chicote, Francisco Manuel
Volonteri, Victoria
Galimberti, Gastón N.
Klamt, Fabio
Duran, Hebe Alicia
author_role author
author2 Rinflerch, Adriana Raquel
Ibañez, Irene Laura
García Chicote, Francisco Manuel
Volonteri, Victoria
Galimberti, Gastón N.
Klamt, Fabio
Duran, Hebe Alicia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv COFILIN-1
MELANOMA
METASTASIS
NUCLEAR LOCALIZATION
PROGNOSIS
topic COFILIN-1
MELANOMA
METASTASIS
NUCLEAR LOCALIZATION
PROGNOSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Melanoma is an aggressive cancer with highly metastatic ability. We propose cofilin-1, a key protein in the regulation of actin dynamics and migration, as a prognostic marker. We determined cofilin-1 levels in a retrospective cohort of patients with melanomas and benign lesions of melanocytes (nevi) by immunohistochemistry. Higher cofilin-1 levels were found in malignant melanoma (MM) with Breslow Index (BI)>2 vs MM with BI<2, melanoma in situ (MIS) and nevi and also in MM with metastasis vs MM without detected metastasis. Kaplan-Meier survival curves were performed, clustering patients according to either the type of melanocytic lesions or cofilin-1 level. Survival curves demonstrated worse prognosis of patients with high vs low cofilin-1 levels. TCGA database analysis of melanoma also showed low survival in patients with upregulated cofilin-1 mRNA vs patients without alteration in CFL1 mRNA expression. As cofilin-1 has a dual function depending on its intracellular localization, we evaluated nuclear and cytoplasmic levels of cofilin-1 in melanoma and nevi samples by immunofluorescence. MM with high Breslow index and metastatic cells not only presented cytoplasmic cofilin-1, but also showed this protein at the nucleus. An increase in nuclear/cytoplasmic cofilin-1 mean fluorescence ratio was observed in MM with BI>2 vs MM with BI<2, MIS and nevi. In conclusion, an association of cofilin-1 levels with malignant features and an inverse correlation with survival were demonstrated. Moreover, this study suggests that not only the higher levels of cofilin-1, but also its nuclear localization can be proposed as marker of worse outcome of patients with melanoma.
Fil: Bracalente, María Candelaria. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rinflerch, Adriana Raquel. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ibañez, Irene Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; Argentina
Fil: García Chicote, Francisco Manuel. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Volonteri, Victoria. Hospital Italiano; Argentina
Fil: Galimberti, Gastón N.. Hospital Italiano; Argentina
Fil: Klamt, Fabio. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Duran, Hebe Alicia. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
description Melanoma is an aggressive cancer with highly metastatic ability. We propose cofilin-1, a key protein in the regulation of actin dynamics and migration, as a prognostic marker. We determined cofilin-1 levels in a retrospective cohort of patients with melanomas and benign lesions of melanocytes (nevi) by immunohistochemistry. Higher cofilin-1 levels were found in malignant melanoma (MM) with Breslow Index (BI)>2 vs MM with BI<2, melanoma in situ (MIS) and nevi and also in MM with metastasis vs MM without detected metastasis. Kaplan-Meier survival curves were performed, clustering patients according to either the type of melanocytic lesions or cofilin-1 level. Survival curves demonstrated worse prognosis of patients with high vs low cofilin-1 levels. TCGA database analysis of melanoma also showed low survival in patients with upregulated cofilin-1 mRNA vs patients without alteration in CFL1 mRNA expression. As cofilin-1 has a dual function depending on its intracellular localization, we evaluated nuclear and cytoplasmic levels of cofilin-1 in melanoma and nevi samples by immunofluorescence. MM with high Breslow index and metastatic cells not only presented cytoplasmic cofilin-1, but also showed this protein at the nucleus. An increase in nuclear/cytoplasmic cofilin-1 mean fluorescence ratio was observed in MM with BI>2 vs MM with BI<2, MIS and nevi. In conclusion, an association of cofilin-1 levels with malignant features and an inverse correlation with survival were demonstrated. Moreover, this study suggests that not only the higher levels of cofilin-1, but also its nuclear localization can be proposed as marker of worse outcome of patients with melanoma.
publishDate 2018
dc.date.none.fl_str_mv 2018-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/102977
Bracalente, María Candelaria; Rinflerch, Adriana Raquel; Ibañez, Irene Laura; García Chicote, Francisco Manuel; Volonteri, Victoria; et al.; Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients; Impact Journals; Oncotarget; 9; 35; 5-2018; 24097-24108
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/102977
identifier_str_mv Bracalente, María Candelaria; Rinflerch, Adriana Raquel; Ibañez, Irene Laura; García Chicote, Francisco Manuel; Volonteri, Victoria; et al.; Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients; Impact Journals; Oncotarget; 9; 35; 5-2018; 24097-24108
1949-2553
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.oncotarget.com/article/25303/
info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.25303
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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