Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/179641 |
Resumo: | 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. |
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Bracalente, CandelariaRinflerch, AdrianaIbañez, Irene LauraGarcia, Francisco M.Volonteri, VictoriaGalimberti, Gastón N.Klamt, FabioDurán, Hebe2018-06-22T02:29:17Z20181949-2553http://hdl.handle.net/10183/179641001069662Melanoma 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.application/pdfengOncotarget. Albany. Vol. 9, no. 35 (May 2018), p. 24097-24108Cofilina 1MelanomaMetástase neoplásicaSinais de localização nuclearCofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patientsEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL001069662.pdf001069662.pdfTexto completo (inglês)application/pdf3118378http://www.lume.ufrgs.br/bitstream/10183/179641/1/001069662.pdfbff80ae2046b5973e6f75ca61d91dfc7MD51TEXT001069662.pdf.txt001069662.pdf.txtExtracted Texttext/plain41677http://www.lume.ufrgs.br/bitstream/10183/179641/2/001069662.pdf.txt1f064767064459fe2107484d617026b6MD5210183/1796412018-06-23 03:31:01.707618oai:www.lume.ufrgs.br:10183/179641Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2018-06-23T06:31:01Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.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, Candelaria Cofilina 1 Melanoma Metástase neoplásica Sinais de localização nuclear |
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 |
author |
Bracalente, Candelaria |
author_facet |
Bracalente, Candelaria Rinflerch, Adriana Ibañez, Irene Laura Garcia, Francisco M. Volonteri, Victoria Galimberti, Gastón N. Klamt, Fabio Durán, Hebe |
author_role |
author |
author2 |
Rinflerch, Adriana Ibañez, Irene Laura Garcia, Francisco M. Volonteri, Victoria Galimberti, Gastón N. Klamt, Fabio Durán, Hebe |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Bracalente, Candelaria Rinflerch, Adriana Ibañez, Irene Laura Garcia, Francisco M. Volonteri, Victoria Galimberti, Gastón N. Klamt, Fabio Durán, Hebe |
dc.subject.por.fl_str_mv |
Cofilina 1 Melanoma Metástase neoplásica Sinais de localização nuclear |
topic |
Cofilina 1 Melanoma Metástase neoplásica Sinais de localização nuclear |
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 |
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2018 |
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001069662 |
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http://hdl.handle.net/10183/179641 |
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eng |
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Oncotarget. Albany. Vol. 9, no. 35 (May 2018), p. 24097-24108 |
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