ニワ　ユキコ   Yukiko Niwa   丹羽　由紀子    所属   医学部 医学科（附属八千代医療センター）    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	PAX5 gene as a novel methylation marker that predicts both clinical outcome and cisplatin sensitivity in esophageal squamous cell carcinoma.
掲載誌名	正式名：Epigenetics 略　 称：Epigenetics ISSNコード：15592308/15592294
掲載区分	国外
巻・号・頁	12(10),pp.865-874
著者・共著者	Kurimoto Keisuke, Hayashi Masamichi, Guerrero-Preston Rafael, Koike Masahiko, Kanda Mitsuro, Hirabayashi Sho, Tanabe Hiroshi, Takano Nao, Iwata Naoki, Niwa Yukiko, Takami Hideki, Kobayashi Daisuke, Tanaka Chie, Yamada Suguru, Nakayama Goro, Sugimoto Hiroyuki, Fujii Tsutomu, Fujiwara Michitaka, Kodera Yasuhiro
発行年月	2017
概要	Therapeutic strategies for esophageal cancer largely depend on histopathological assessment. To select appropriate treatments of individual patients, we examined the background molecular characteristics of tumor malignancy and sensitivity to multidisciplinary therapy. Seventy-eight surgically-resected esophageal squamous cell carcinoma (ESCC) cases during 2001-2013 were examined. PAX5, a novel gene methylation marker in ESCC, was evaluated in the specimens, as methylation of this gene was identified as an extremely tumor-specific event in squamous cell carcinogenesis of head and neck. PAX5 methylation status was evaluated by quantitative MSP (QMSP) assays. Mean QMSP value was 15.7 (0-136.3) in ESCCs and 0.3 (0-8.6) in adjacent normal tissues (P < 0.001). The 78 cases were divided into high QMSP value (high QMSP, n = 26) and low QMSP value (low QMSP, n = 52). High QMSP cases were significantly associated with downregulated PAX5 expression (P = 0.040), and showed significantly poor recurrence-free survival [Hazard Ratio (HR) = 2.84; P = 0.005; 95% Confidence Interval (CI): 1.39-5.81] and overall survival (HR = 3.23; P = 0.002; 95%CI: 1.52-7.01) in multivariable analyses with histopathological factors. PAX5-knockdown cells exhibited significantly increased cell proliferation and cisplatin resistance. PAX5 gene methylation can predict poor survival outcomes and cisplatin sensitivity in ESCCs and could be a useful diagnostic tool for cancer therapy selection.
DOI	10.1080/15592294.2017.1365207
PMID	29099287