教員業績データベース |
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論文種別 | 原著 |
言語種別 | 英語 |
査読の有無 | 査読なし |
表題 | Identification of keratin 19-positive cancer stem cells associating human hepatocellular carcinoma using CYFRA 21-1 |
掲載誌名 | 正式名:Cancer medicine 略 称:Cancer Med ISSNコード:2045-7634(Electronic)2045-7634(Linking) |
掲載区分 | 国外 |
巻・号・頁 | 6(11),pp.2531-40 |
著者・共著者 | Kawai Takayuki, Yasuchika Kentaro, Ishii Takamichi, Katayama Hokahiro, Yoshitoshi Elena Yukie, Ogiso Satoshi, Minami Takahito, Miyauchi Yuya, Kojima Hidenobu, Yamaoka Ryoya, Kita Sadahiko, Yasuda Katsutaro, Sasaki Naoya, Fukumitsu Ken, Hatano Etsuro, Uemoto Shinji |
発行年月 | 2017/11 |
概要 | The current lack of an easily measurable surrogate marker of cancer stem cells (CSCs) prevents the clinical application of CSCs for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker associated with transforming growth factor beta (TGFβ)/Smad signaling, and that K19+ HCC-CSCs could be a new therapeutic target of TGFβ receptor 1 inhibitor LY2157299. In this study, we examined whether K19+ HCC-CSCs can be tracked using cytokeratin 19 fragment CYFRA 21-1. In 147 HCC patients who underwent curative resection and evaluated K19 expression by immunohistochemistry, preoperative serum CYFRA 21-1 levels were significantly higher in K19+ patients than in K19- patients (P < 0.01). Receiver operating characteristic analyses revealed that serum CYFRA 21-1 was the statistically significant and the most sensitive predictor of tumor K19 expression among preoperative laboratory test values (P < 0.001). In HCC cells encoding with a K19 promoter-driven enhanced green fluorescent protein, fluorescence-activated cell sorting (FACS)-isolated K19+ cells displayed significantly higher levels of supernatant CYFRA 21-1 than K19- cells (P < 0.01). Gain/loss of K19 function experiments confirmed that CYFRA 21-1 levels were regulated by K19 function in HCC cells. Furthermore, CYFRA 21-1 levels reflected the treatment efficacy of LY2157299 in K19+ cells. In conclusion, CYFRA 21-1 can be used to predict K19 expression in HCC, and should thereby aid in the development of novel therapeutic strategies targeting K19+ HCC-CSCs. |
DOI | 10.1002/cam4.1211 |
PMID | 28965351 |