FGF5 methylation is a sensitivity marker of esophageal squamous cell carcinoma to definitive chemoradiotherapy.
Sci Rep
; 9(1): 13347, 2019 09 16.
Article
en En
| MEDLINE
| ID: mdl-31527639
ABSTRACT
Definitive chemoradiotherapy (dCRT) is the major treatment for esophageal squamous cell carcinoma (ESCC), and prediction of the response to dCRT is important so as not to miss an opportunity to cure an ESCC. Nevertheless, few validated markers are available. Here, we aimed to identify a highly reproducible marker using multi-layer omics analysis. 117 ESCC samples from 67 responders and 50 non-responders were divided into screening, validation, and re-validation sets. In the screening cohort (n = 41), somatic mutations in 114 genes showed no association with dCRT response. Genome-wide DNA methylation analysis using Infinium HumanMethylation450 BeadChip array identified four genic regions significantly associated with dCRT response. Among them, FGF5 methylation was validated to be associated with dCRT response (n = 34; P = 0.001), and further re-validated (n = 42; P = 0.020) by bisulfite-pyrosequencing. The sensitivity and specificity in the combined validation and re-validation sets (n = 76) were 45% and 90%, respectively, by using the cut-off value established in the screening set, and FGF5 methylation had predictive power independent from clinicopathological parameters. In ESCC cell lines, FGF5 promoter methylation repressed its expression. FGF5 expression was induced by cisplatin (CDDP) treatment in three unmethylated cell lines, but not in two methylated cell lines. Exogenous FGF5 overexpression in a cell line with its methylation conferred resistance to CDDP. In non-cancerous esophageal tissues, FGF5 was not expressed, and its methylation was present in a small fraction of cells. These results showed that FGF5 methylation is a validated marker for ESCC sensitivity to dCRT.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tolerancia a Radiación
/
Neoplasias Esofágicas
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Resistencia a Antineoplásicos
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Metilación de ADN
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Factor 5 de Crecimiento de Fibroblastos
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Carcinoma de Células Escamosas de Esófago
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Sci Rep
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón