Novel candidate factors predicting the effect of S-1 adjuvant chemotherapy of pancreatic cancer

• Project/Area Number: 18K16337
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Tohoku University
• Principal Investigator: Ariake Kyohei 東北大学, 大学病院, 助教 (10754921)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 膵癌 / 抗癌剤感受性 / プロテオミクス / CD-DST / S-1 / 5-FU / 抗癌剤 / 感受性 / CD-DST法

Outline of Final Research Achievements

The aim of this study was to discover novel biomarkers to predict chemosensitivity based on the CD-DST results.Proteomics analysis was performed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Candidate proteins were validated in patients with 5-FU CD-DST results via immunohistochemistry (IHC). The relationships between the candidate proteins and the effect of the adjuvant S-1 were investigated via IHC.Among the 2696 proteins extracted by LC-MS/MS, C1TC and SAHH could accurately predict the CD-DST results. Recurrence-free survival (RFS) was significantly improved in the IHC-positive group compared with the IHC-negative group in both factors. The negative group did not show a significant difference from the group that did not receive S-1. Thus C1TC and SAHH have been shown to be useful biomarkers for predicting 5-FU sensitivity as a substitute for the CD-DST in adjuvant chemotherapy for PDAC.

Academic Significance and Societal Importance of the Research Achievements

膵癌は切除後S-1による半年間の補助治療が推奨されているが，補助治療による予後改善効果が得られない症例が少なからず存在する．本研究によって得られた因子は，膵癌切除後のS-1による上乗せ効果が期待できない症例の選別に有効である可能性がある．また得られた2因子はいずれも１炭素代謝(葉酸代謝及びメチオニン代謝)に関与する因子である．本因子の欠落により，S-1の効果を発揮する上で必要とされるメチレンテトラヒドロ葉酸の合成が低下することで感受性が低下するものと考えられた．本研究結果は抗癌剤のレジメン変更についての検討や，感受性を高めるために必要なアプローチを検討する上でも有用な研究になったと考えられた．

Research Products

• [Journal Article] Novel candidate factors predicting the effect of S-1 adjuvant chemotherapy of pancreatic cancer (2021)
  • Author(s): Mitachi Katsutaka、Ariake Kyohei、Shima Hiroki、Sato Satoko、Miura Takayuki、Maeda Shimpei、Ishida Masaharu、Mizuma Masamichi、Ohtsuka Hideo、Kamei Takashi、Igarashi Kazuhiko、Unno Michiaki
  • Journal Title: Scientific Reports Volume: 11 Issue: 1
  • DOI: 10.1038/s41598-021-86099-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Preceding Systemic Chemotherapy for Patients with Pancreatic Ductal Adenocarcinoma with Positive Peritoneal Cytology Provides Survival Benefit Compared with Up-Front Surgery (2021)
  • Author(s): Ariake Kyohei、Mizuma Masamichi、Motoi Fuyuhio、Maeda Shimpei、Morikawa Takanori、Ishida Masaharu、Ohtsuka Hideo、Aoki Shuichi、Miura Takayuki、Takadate Tatsuyuki、Nakagawa Kei、Kamei Takashi、Unno Michiaki
  • Journal Title: Annals of Surgical Oncology Volume: - Issue: 11 Pages: 6246-6254
  • DOI: 10.1245/s10434-021-09718-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] FBXW7 modulates malignant potential and cisplatin-induced apoptosis in cholangiocarcinoma through NOTCH1 and MCL1 (2018)
  • Author(s): Mori Akiko、Masuda Kunihiro、Ohtsuka Hideo、Shijo Masahiro、Ariake Kyohei、Fukase Koji、Sakata Naoaki、Mizuma Masamichi、Morikawa Takanori、Hayashi Hiroki、Nakagawa Kei、Motoi Fuyuhiko、Naitoh Takeshi、Fujishima Fumiyoshi、Unno Michiaki
  • Journal Title: Cancer Science Volume: 109 Issue: 12 Pages: 3883-3895
  • DOI: 10.1111/cas.13829
  • Peer Reviewed / Open Access
• [Presentation] 抗癌剤感受性試験に基づいた膵癌術後補助療法におけるS-1の新規効果予測因子の同定 (2021)
  • Author(s): 三田地克昂、有明恭平、吉町信吾、青木修一、畠 達夫、三浦孝之、 高舘達之、前田晋平、川口 桂、益田邦洋、石田晶玄、大塚英郎、水間正道、 中川 圭、森川孝則、大沼 忍、石田孝宣、亀井 尚、海野倫明
  • Organizer: 第121回日本外科学会学術集会
• [Presentation] 膵癌術後補助化学療法の効果予測に有用な新規バイオマーカーの発見 (2020)
  • Author(s): 三田地克昂、有明恭平、島弘季、吉町信吾、三浦孝之、前田晋平、 石田晶玄、大塚英郎、水間正道、 中川 圭、林洋毅，森川孝則、五十嵐和彦、亀井 尚、海野倫明
  • Organizer: 第79回日本癌学会学術総会
• [Presentation] CD-DST法を用いた抗癌剤感受性試験は膵癌術後補助治療の有効性を予測する (2018)
  • Author(s): 有明恭平
  • Organizer: 第49回日本膵臓学会大会
• [Presentation] Collagen Gel Droplet–embedded culture drug sensitivity test predicts adjuvant chemotherapy efficacy in pancreatic cancer (2018)
  • Author(s): Kyohei Ariake
  • Organizer: IASGO WORLD CONGRESS 2018
  • Int'l Joint Research