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Tumor metabolic alterations after neoadjuvant chemoradiotherapy predict postoperative recurrence in patients with pancreatic cancer.
Wada, Yukiko; Okano, Keiichi; Sato, Kiyotoshi; Sugimoto, Masahiro; Shimomura, Ayaka; Nagao, Mina; Matsukawa, Hiroyuki; Ando, Yasuhisa; Suto, Hironobu; Oshima, Minoru; Kondo, Akihiro; Asano, Eisuke; Kishino, Takayoshi; Kumamoto, Kensuke; Kobara, Hideki; Kamada, Hideki; Masaki, Tsutomu; Soga, Tomoyoshi; Suzuki, Yasuyuki.
Afiliación
  • Wada Y; Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Kagawa, Japan.
  • Okano K; Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Kagawa, Japan.
  • Sato K; Institute for Advanced Biosciences, Keio University, Kakuganji, Tsuruoka, Japan.
  • Sugimoto M; Institute for Advanced Biosciences, Keio University, Kakuganji, Tsuruoka, Japan.
  • Shimomura A; Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Kagawa, Japan.
  • Nagao M; Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Kagawa, Japan.
  • Matsukawa H; Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Kagawa, Japan.
  • Ando Y; Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Kagawa, Japan.
  • Suto H; Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Kagawa, Japan.
  • Oshima M; Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Kagawa, Japan.
  • Kondo A; Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Kagawa, Japan.
  • Asano E; Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Kagawa, Japan.
  • Kishino T; Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Kagawa, Japan.
  • Kumamoto K; Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Kagawa, Japan.
  • Kobara H; Department of Gastroenterology and Neurology, Kagawa University, Takamatsu, Kagawa, Japan.
  • Kamada H; Department of Gastroenterology and Neurology, Kagawa University, Takamatsu, Kagawa, Japan.
  • Masaki T; Department of Gastroenterology and Neurology, Kagawa University, Takamatsu, Kagawa, Japan.
  • Soga T; Institute for Advanced Biosciences, Keio University, Kakuganji, Tsuruoka, Japan.
  • Suzuki Y; Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Kagawa, Japan.
Jpn J Clin Oncol ; 52(8): 887-895, 2022 08 05.
Article en En | MEDLINE | ID: mdl-35523689
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Jpn J Clin Oncol Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Jpn J Clin Oncol Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido