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Cell Cycle ; 15(11): 1462-70, 2016 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-27105345

RESUMEN

BRAF mutations are known drivers of melanoma development and, recently, were also described as players in the Warburg effect, while this reprogramming of energy metabolism has been identified as a possible strategy for treating melanoma patients. Therefore, the aim of this work was to evaluate the expression and prognostic value of a panel of glycolytic metabolism-related proteins in a series of melanomas. The immunohistochemical expression of MCT1, MCT4, GLUT1, and CAIX was evaluated in 356 patients presenting melanoma and 20 patients presenting benign nevi. Samples included 20 benign nevi, 282 primary melanomas, 117 lymph node and 54 distant metastases samples. BRAF mutation was observed in 29/92 (31.5%) melanoma patients and 17/20 (85%) benign nevi samples. NRAS mutation was observed in 4/36 (11.1%) melanoma patients and 1/19 (5.3%) benign nevi samples. MCT4 and GLUT1 expression was significantly increased in metastatic samples, and MCT1, MCT4 and GLUT1 were significantly associated with poor prognostic variables. Importantly, MCT1 and MCT4 were associated with shorter overall survival. In conclusion, the present study brings new insights on metabolic aspects of melanoma, paving the way for the development of new-targeted therapies.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Melanoma/genética , Transportadores de Ácidos Monocarboxílicos/genética , Proteínas Musculares/genética , Neoplasias/genética , Nevo/genética , Neoplasias Cutáneas/genética , Simportadores/genética , Adulto , Anciano , Anhidrasa Carbónica IX/genética , Anhidrasa Carbónica IX/metabolismo , Estudios de Casos y Controles , Metabolismo Energético/genética , Femenino , GTP Fosfohidrolasas/genética , GTP Fosfohidrolasas/metabolismo , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 1/metabolismo , Humanos , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Melanoma/diagnóstico , Melanoma/mortalidad , Melanoma/patología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Musculares/metabolismo , Neoplasias/diagnóstico , Neoplasias/mortalidad , Neoplasias/patología , Nevo/diagnóstico , Nevo/mortalidad , Nevo/patología , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Transducción de Señal , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Análisis de Supervivencia , Simportadores/metabolismo
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