Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients
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Candelaria Bracalente1,2, Adriana R. Rinflerch3, Irene L. Ibañez1,2, Francisco M. García4, Victoria Volonteri5, Gastón N. Galimberti3, Fabio Klamt6 and Hebe Durán1,2,4
1Gerencia de Investigación y Aplicaciones, Comisión Nacional de Energía Atómica, (B1650KNA) San Martín, Buenos Aires, Argentina
2Consejo Nacional de Investigaciones Científicas y Técnicas, (C1425FQB) CABA, Buenos Aires, Argentina
3Dermatología Experimental, Servicio de Dermatología, Hospital Italiano de Buenos Aires, (C1199ABB) CABA, Buenos Aires, Argentina
4Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, Campus Miguelete, (B1650HMP) San Martín, Buenos Aires, Argentina
5Servicio de Anatomía Patológica, Hospital Italiano de Buenos Aires, (C1199ABB) CABA, Buenos Aires, Argentina
6Laboratório de Bioquímica Celular, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, (90035 003), Porto Alegre, Brazil
Hebe Durán, email: [email protected]
Keywords: cofilin-1; melanoma; metastasis; nuclear localization; prognosis
Received: August 30, 2017 Accepted: April 05, 2018 Published: May 08, 2018
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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