2024-03-29T11:59:27Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00026249
2023-01-16T04:43:38Z
499:500:501
Significance of SYT8 For the Detection, Prediction, and Treatment of Peritoneal Metastasis From Gastric Cancer
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
open access
This is a non-final version of an article published in final form in (Annals of Surgery. v.267, n.3, 2018, p.495-503).
biomarker
gastric cancer
peritoneal metastasis
synaptotagmin VIII
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 growth of peritoneal nodules and prolonged survival of mice engrafted with GC cells. Conclusions: SYT8 represents a promising target for the detection, prediction, and treatment of peritoneal metastasis of GC.
ファイル公開:2019-03-01
Wolters Kluwer Health
2018-03
eng
journal article
AM
http://hdl.handle.net/2237/00028453
https://nagoya.repo.nii.ac.jp/records/26249
https://doi.org/10.1097/SLA.0000000000002096
0003-4932
Annals of Surgery
267
3
495
503
https://nagoya.repo.nii.ac.jp/record/26249/files/Manuscript_repository20180807.pdf
application/pdf
1.4 MB
2019-03-01