Tumor metabolic alterations after neoadjuvant chemoradiotherapy predict postoperative recurrence in patients with pancreatic cancer

Yukiko Wada, Keiichi Okano, Kiyotoshi Sato, Masahiro Sugimoto, Ayaka Shimomura, Mina Nagao, Hiroyuki Matsukawa, Yasuhisa Ando, Hironobu Suto, Minoru Oshima, Akihiro Kondo, Eisuke Asano, Takayoshi Kishino, Kensuke Kumamoto, Hideki Kobara, Hideki Kamada, Tsutomu Masaki, Tomoyoshi Soga, Yasuyuki Suzuki

研究成果: Article査読

抄録

Objective: We investigated the metabolic changes in pancreatic ductal adenocarcinoma to identify the mechanisms of treatment response of neoadjuvant chemoradiation therapy. Methods: Frozen tumor and non-neoplastic pancreas tissues were prospectively obtained from 88 patients with pancreatic ductal adenocarcinoma who underwent curative-intent surgery. Sixty-two patients received neoadjuvant chemoradiation therapy and 26 patients did not receive neoadjuvant therapy (control group). Comprehensive analysis of metabolites in tumor and non-neoplastic pancreatic tissue was performed by capillary electrophoresis-mass spectrometry. Results: Capillary electrophoresis-mass spectrometry detected 90 metabolites for analysis among more than 500 ionic metabolites quantified. There were significant differences in 27 tumor metabolites between the neoadjuvant chemoradiation therapy and control groups. There were significant differences in eight metabolites [1-MethylnNicotinamide, Carnitine, Glucose, Glutathione (red), N-acetylglucosamine 6-phosphate, N-acetylglucosamine 1-phosphate, UMP, Phosphocholine] between good responder and poor responder for neoadjuvant chemoradiation therapy. Among these metabolites, phosphocholine, Carnitine and Glutathione were associated with recurrence-free survival only in the neoadjuvant chemoradiation therapy group. Microarray confirmed marked gene suppression of choline transporters [CTL1-4 (SLC44A1-44A4)] in pancreatic ductal adenocarcinoma tissue of neoadjuvant chemoradiation therapy group. Conclusion: The present study identifies several important metabolic consequences and potential neoadjuvant chemoradiation therapy targets in pancreatic ductal adenocarcinoma. Choline metabolism is one of the key pathways involved in recurrence of the patients with pancreatic ductal adenocarcinoma who received neoadjuvant chemoradiation therapy.

本文言語English
ページ(範囲)879-887
ページ数9
ジャーナルJapanese journal of clinical oncology
52
8
DOI
出版ステータスPublished - 2022 8月 1

ASJC Scopus subject areas

  • 腫瘍学
  • 放射線学、核医学およびイメージング
  • 癌研究

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