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ニワ ユキコ
NIWA Yukiko
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 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Significance of SYT8 For the Detection, Prediction, and Treatment of Peritoneal Metastasis From Gastric Cancer. |
| 掲載誌名 | 正式名：Annals of surgery 略 称：Ann Surg ISSNコード：15281140/00034932 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 267(3),pp.495-503 |
| 著者・共著者 | Kanda Mitsuro, Shimizu Dai, Tanaka Haruyoshi, Tanaka Chie, Kobayashi Daisuke, Hayashi Masamichi, Iwata Naoki, Niwa Yukiko, Yamada Suguru, Fujii Tsutomu, Sugimoto Hiroyuki, Murotani Kenta, Fujiwara Michitaka, Kodera Yasuhiro |
| 発行年月 | 2018/03 |
| 概要 | OBJECTIVE:To develop novel diagnostic and therapeutic targets specific for peritoneal metastasis of gastric cancer (GC).BACKGROUND:Advanced GC frequently recurs because of undetected micrometastases even after curative resection. Peritoneal metastasis has been the most frequent recurrent pattern after gastrectomy and is incurable.METHODS:We conducted a recurrence pattern-specific transcriptome analysis in an independent cohort of 16 patients with stage III GC who underwent curative gastrectomy and adjuvant S-1 for screening candidate molecules specific for peritoneal metastasis of GC. Next, another 340 patients were allocated to discovery and validation sets (1:2) to evaluate the diagnostic and predictive value of the candidate molecule. The results of quantitative reverse-transcription PCR and immunohistochemical analysis were correlated with clinical characteristics and survival. The effects of siRNA-mediated knockdown on phenotype and fluorouracil sensitivity of GC cells were evaluated in vitro, and the therapeutic effects of siRNAs were evaluated using a mouse xenograft model.RESULTS:Synaptotagmin VIII (SYT8) was identified as a candidate biomarker specific to peritoneal metastasis. In the discovery set, the optimal cut-off of SYT8 expression was established as 0.005. Expression levels of SYT8 mRNA in GC tissues were elevated in the validation set comprising patients with peritoneal recurrence or metastasis. SYT8 levels above the cut-off value were significantly and specifically associated with peritoneal metastasis, and served as an independent prognostic marker for peritoneal recurrence-free survival of patients with stage II/III GC. The survival difference between patients with SYT8 levels above and below the cut-off was associated with patients who received adjuvant chemotherapy. Inhibition of SYT8 expression by GC cells correlated with decreased invasion, migration, and fluorouracil resistance. Intraperitoneal administration of SYT8-siRNA inhibited the grow |
| DOI | 10.1097/SLA.0000000000002096 |
| PMID | 28026832 |