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Journal of Cancer Research and Clinical Oncology

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01.03.2015 | Original Article – Cancer Research

ZNF695 methylation predicts a response of esophageal squamous cell carcinoma to definitive chemoradiotherapy

verfasst von: Takamasa Takahashi, Satoshi Yamahsita, Yasunori Matsuda, Takayoshi Kishino, Takeshi Nakajima, Ryoji Kushima, Ken Kato, Hiroyasu Igaki, Yuji Tachimori, Harushi Osugi, Masato Nagino, Toshikazu Ushijima

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 3/2015

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Abstract

Purpose

Definitive chemoradiotherapy (dCRT) is one of the standard treatments for esophageal squamous cell carcinoma. Patients with a response to dCRT have a better prognosis than those resistant to dCRT while survival benefits for patients with residual tumors are limited. Nevertheless, few molecular markers to predict the response to dCRT are currently available. Here, we aimed to establish a DNA methylation marker to predict the response to dCRT.

Methods

A total of 104 patients were divided into screening (n = 43) and validation (n = 61) sets. A genome-wide DNA methylation analysis was performed using an Infinium HumanMethylation450 BeadChip array. Methylation levels were measured by quantitative methylation-specific PCR and normalized by the fraction of cancer cells in a sample.

Results

The genome-wide methylation analysis of seven responders and eight non-responders identified 18 genomic regions specifically (un)methylated in the responders. Among these, methylation of the promoter CpG island of ZNF695 was significantly associated with the response to dCRT in the screening set (P = 0.004), and a cutoff value was determined. In the validation set, the association was successfully validated (P = 0.021), and a high specificity (90 %) for the prediction of responders was obtained using the prefixed cutoff value. In addition, a multivariate analysis showed that ZNF695 methylation was an independent predictive factor for the response to dCRT (OR 7.55, 95 % CI 2.12–26.9, P = 0.002).

Conclusion

ZNF695 methylation was significantly associated with the response to dCRT and is a promising predictive marker for the response to dCRT.

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Titel: ZNF695 methylation predicts a response of esophageal squamous cell carcinoma to definitive chemoradiotherapy
verfasst von: Takamasa Takahashi
Satoshi Yamahsita
Yasunori Matsuda
Takayoshi Kishino
Takeshi Nakajima
Ryoji Kushima
Ken Kato
Hiroyasu Igaki
Yuji Tachimori
Harushi Osugi
Masato Nagino
Toshikazu Ushijima
Publikationsdatum: 01.03.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 3/2015
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-014-1841-x

Springer Medizin

ZNF695 methylation predicts a response of esophageal squamous cell carcinoma to definitive chemoradiotherapy