New classification of gastric cancer based on genome analysis for precision medicine

• Project/Area Number: 17H04280
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Gifu University
• Principal Investigator: YOSHIDA KAZUHIRO 岐阜大学, 大学院医学系研究科, 教授 (50230727)
• Co-Investigator(Kenkyū-buntansha): 奥田 修二郎 新潟大学, 医歯学系, 准教授 (00512310) ; 二村 学 岐阜大学, 大学院医学系研究科, 准教授 (10415515) ; 大島 貴 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), その他部局等, 部長 (10448665) ; 北川 雄光 慶應義塾大学, 医学部(信濃町), 教授 (20204878) ; 沖 英次 九州大学, 大学病院, 講師 (70380392)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000); Fiscal Year 2017: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: 胃癌 / 癌ゲノム解析 / Precision Medicine / Precision medicine / ゲノム / がんゲノム / 新臨床分類 / NGS / ゲノム分類 / 薬剤感受性

Outline of Final Research Achievements

To clarify the genomic character of Japanese gastric cancer (GC), we analyzed genomic alterations of domestic GC tissues by CancerPlex, which is a cancer genome panel produced by KEW group in US. Of 207 surgically dissected GCs, 93.7% of GCs revealed at least one genomic alteration. Based on the genomic classifications by TCGA, we classified 207 cases into 4 subtypes (EBV:4%, MSI:8%, CIN:58%, GS:30%). Among them, population of EBV, MSI subtypes were less compared with TCGA data. These results may be associated with rare EBV infection or frequent H.pylori infection. We should further make an effort to enlarge the scale of genomic database in Japan.

Academic Significance and Societal Importance of the Research Achievements

本邦における胃癌の発生頻度・死亡率は以前から高く、現在においても依然上位にランクされます。胃癌の発生には多くの遺伝子要因が関与していますが、腫瘍の個体差ごとに遺伝子変化が異なり、未解決の部分も多く見られます。今回、本邦の胃癌においても90%以上でがんゲノムの異常が指摘されました。この結果はゲノム医療の有用性を示唆するものであり、ゲノム医療の均てん化を目指すうえでデータベースの更なる充実は必要と考えられます。

Research Products

• [Journal Article] A subanalysis of Japanese patients in a randomized, double-blind, placebo-controlled, phase 3 trial of nivolumab for patients with advanced gastric or gastro-esophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2). (2019)
  • Author(s): Kato K, Satoh T, Muro K, Yoshikawa T, Tamura T, Hamamoto Y, Chin K, Minashi K, Tsuda M, Yamaguchi K, Machida N, Esaki T, Goto M, Komatsu Y, Eguchi Nakajima T, Sugimoto N, Yoshida K, Oki E, Nishina T, Tsuji A, Fujii H, Kunieda K, Saitoh S, Omuro Y, Azuma M, Iwamoto Y, Taku K, Fushida S, Chen LT, Kang YK, Boku N
  • Journal Title: Gastric Cancer Volume: 22(2) Issue: 2 Pages: 344-354
  • DOI: 10.1007/s10120-018-0899-6
  • NAID: 40021832780
  • Peer Reviewed
• [Journal Article] Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial (2019)
  • Author(s): Yoshida Kazuhiro、Kodera Yasuhiro、Kochi Mitsugu、Ichikawa Wataru、Kakeji Yoshihiro、Sano Takeshi、Nagao Narutoshi、Takahashi Masazumi、Takagane Akinori、Watanabe Takuya、Kaji Masahide、Okitsu Hiroshi、Nomura Takashi、Matsui Takanori、Yoshikawa Takaki、Matsuyama Jin、Yamada Makoto、Ito Seiji
  • Journal Title: Journal of Clinical Oncology Volume: － Issue: 15 Pages: 1296-1304
  • DOI: 10.1200/jco.18.01138
  • Peer Reviewed
• [Journal Article] Synthetic miR-143 Inhibits Growth of HER2-Positive Gastric Cancer Cells by Suppressing KRAS Networks Including DDX6 RNA Helicase (2019)
  • Author(s): Tokumaru Yoshihisa、Tajirika Toshihiro、Sugito Nobuhiko、Kuranaga Yuki、Shinohara Haruka、Tsujino Takuya、Matsuhashi Nobuhisa、Futamura Manabu、Akao Yukihiro、Yoshida Kazuhiro
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 7 Pages: 1697-1697
  • DOI: 10.3390/ijms20071697
  • Peer Reviewed / Open Access
• [Journal Article] Perioperative risk calculator for distal gastrectomy predicts overall survival in patients with gastric cancer. (2019)
  • Author(s): Takeuchi M, Kawakubo H, Mayanagi S, Suzuki Y, Okabayashi K, Yamashita T, Kamiya S, Irino T, Fukuda K, Nakamura R, Suda K, Wada N, Takeuchi H, Kitagawa Y
  • Journal Title: Gastric Cancer Volume: 22(3) Issue: 3 Pages: 624-631
  • DOI: 10.1007/s10120-018-0896-9
  • NAID: 40021884179
  • Peer Reviewed
• [Journal Article] Survival Outcomes of Two Phase 2 Studies of Adjuvant Chemotherapy with S-1 Plus Oxaliplatin or Capecitabine Plus Oxaliplatin for Patients with Gastric Cancer After D2 Gastrectomy. (2019)
  • Author(s): Nakamura Y, Yamanaka T, Chin K, Cho H, Katai H, Terashima M, Misawa K, Hirao M, Yoshida K, Oki E, Sasako M, Emi Y, Bando H, Kawashima Y, Fukunaga T, Gotoh M, Ishibashi T, Shitara K.
  • Journal Title: Annals of Surgical Oncology Volume: 26(2) Issue: 2 Pages: 465-472
  • DOI: 10.1245/s10434-018-7063-8
  • Peer Reviewed
• [Journal Article] Clinical Significance of PRKCI Gene Expression in Cancerous Tissue in Patients With Gastric Cancer (2019)
  • Author(s): HASHIMOTO ITARU、SAKAMAKI KENTARO、OUE NAOHIDE、KIMURA YAYOI、HIROSHIMA YUKIHIKO、HARA KENTARO、MAEZAWA YUKIO、KANO KAZUKI、AOYAMA TORU、YAMADA TAKANOBU、YAMAMOTO NAOTO、OGATA TAKASHI、ITO HIROYUKI、SHIOZAWA MANABU、MORINAGA SOICHIRO、RINO YASUSHI、YASUI WATARU、MASUDA MUNETAKA、MIYAGI YOHEI、OSHIMA TAKASHI
  • Journal Title: Anticancer Research Volume: 39 Issue: 10 Pages: 5715-5720
  • DOI: 10.21873/anticanres.13771
  • Peer Reviewed
• [Journal Article] Precision medicine に向けたゲノム解析に基づく胃癌新分類の試み (2018)
  • Author(s): 二村 学、吉田 和弘
  • Journal Title: BIO Clinica Volume: 33 Pages: 549-554
  • Peer Reviewed
• [Presentation] Pathogenic germline BRCA1/2 mutations and familial predisposition to gastric cancer (2018)
  • Author(s): Ichikawa H, Nagahashi M, Shimada Y, Hanyu T, Ishikawa T, Kano Y, Muneoka Y, Takizawa K, Sakata J, Kobayashi T, Kameyama H, Nakagawa S, Kitagawa Y, Yoshida K, Oki E, Wakai T
  • Organizer: 第90回日本胃癌学会総会
• [Presentation] Tumor mutation burden in triple negative breast cancer patients in Japan (2018)
  • Author(s): Masayuki Nagahashi
  • Organizer: ASCO 2018