RESUMEN
The methylation status of the IGFBP-3 gene is strongly associated with cisplatin sensitivity in patients with non-small cell lung cancer (NSCLC). In this study, we found in vitro evidence that linked the presence of an unmethylated promoter with poor response to radiation. Our data also indicate that radiation might sensitize chemotherapy-resistant cells by reactivating IGFBP-3-expression through promoter demethylation, inactivating the PI3K/AKT pathway. We also explored the IGFBP-3 methylation effect on overall survival (OS) in a population of 40 NSCLC patients who received adjuvant therapy after R0 surgery. Our results indicate that patients harboring an unmethylated promoter could benefit more from a chemotherapy schedule alone than from a multimodality therapy involving radiotherapy and platinum-based treatments, increasing their OS by 2.5 y (p = .03). Our findings discard this epi-marker as a prognostic factor in a patient population without adjuvant therapy, indicating that radiotherapy does not improve survival for patients harboring an unmethylated IGFBP-3 promoter.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Neoplasias Pulmonares/radioterapia , Regiones Promotoras Genéticas , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Línea Celular Tumoral/efectos de la radiación , Supervivencia Celular/genética , Supervivencia Celular/efectos de la radiación , Terapia Combinada , Metilación de ADN , Femenino , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Fosforilación/efectos de los fármacos , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
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