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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)879-887
Number of pages9
JournalJapanese journal of clinical oncology
Volume52
Issue number8
DOIs
Publication statusPublished - 2022 Aug 1

Keywords

  • CE-MS
  • PDAC
  • choline
  • metabolomics
  • neoadjuvant therapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Fingerprint

Dive into the research topics of 'Tumor metabolic alterations after neoadjuvant chemoradiotherapy predict postoperative recurrence in patients with pancreatic cancer'. Together they form a unique fingerprint.

Cite this