Oncotarget

Research Papers:

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

Candelaria Bracalente, Adriana R. Rinflerch, Irene L. Ibañez, Francisco M. García, Victoria Volonteri, Gastón N. Galimberti, Fabio Klamt and Hebe Durán _

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Oncotarget. 2018; 9:24097-24108. https://doi.org/10.18632/oncotarget.25303

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Abstract

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

Correspondence to:

Hebe Durán, email: hduran@cnea.gov.ar

Keywords: cofilin-1; melanoma; metastasis; nuclear localization; prognosis

Received: August 30, 2017    Accepted: April 05, 2018    Published: May 08, 2018

ABSTRACT

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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