Development of personalized medicine for prostate cancer by TP53 signature diagnostic method

• Project/Area Number: 16K11029
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Juntendo University
• Principal Investigator: Kato Shunsuke 順天堂大学, 医学(系)研究科(研究院), 教授 (40312657)
• Co-Investigator(Kenkyū-buntansha): 堀江 重郎 順天堂大学, 医学(系)研究科(研究院), 教授 (40190243)
• Research Collaborator: YAMAGUCHI Shigeo 順天堂大学, 医学(系)研究科, 助教 (40747797)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: TP53 / 前立腺がん / 発現プロファイル / 予後予測バイオマーカー / 予後予測診断 / p53 / 予後予測

Outline of Final Research Achievements

Using 50 clinical specimens of prostate cancer, the usefulness of the gene expression profile TP53 signature as a prognostic biomarker was evaluated. As a result, recurrence risk is high in cases which TP53 signature was judged to be a mutant type, comparing to a wild type. TP53 signature was revealed extremely high ability to predict recurrence even in comparison with clinical factors such as Gleason score. In addition, as a result of analyzing the molecular features of TP53 signature mutant type using public omics database, it is clarified that it has features such as increase in copy number of MDM2 and MDM4, low dependency of androgen hormone, and high tumor mutation burden. These results provide the basic data for development of new treatment for the patients with TP53 signature mutant type.

Academic Significance and Societal Importance of the Research Achievements

早期前立腺がんの予後予測に、遺伝子発現プロファイルTP53signatureが有用であることを明らかにしたはじめての研究であり、臨床因子に加えてTP53 signatureを解析することで、過小・過剰医療を回避することができ、より患者に合った精緻医療の実現が可能となることが期待される結果を得ることができた。さらに予後不良群であるTP53 signature変異型の前立腺がん細胞の分子生物学的な特徴がオミックスデータから明らかになり、これら患者群に対する新規治療法の開発につながる基礎的データの収集ができた。

Research Products

• [Journal Article] Multicenter experience with large panel next-generation sequencing in patients with advanced solid cancers in Japan. (2019)
  • Author(s): Kato S, Hayashi T, Suehara Y, Hamanoue H, Yamanaka S, Ichikawa Y, Higurashi T, Ohashi K, Yamaguchi S, Nozaki Y, Terao Y, Saito T.
  • Journal Title: Jpn J Clin Oncol Volume: 49(2) Issue: 2 Pages: 174-182
  • DOI: 10.1093/jjco/hyy173
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular and clinical features of the TP53 signature gene expression profile in early-stage breast cancer. (2018)
  • Author(s): Yamaguchi S, Takahashi S, Mogushi K, Izumi Y, Nozaki Y, Nomizu T, Kakugawa Y, Ishida T, Ohuchi N, Ishioka C, Kato S.
  • Journal Title: Oncotarget Volume: 9(18) Issue: 18 Pages: 14193-14206
  • DOI: 10.18632/oncotarget.24447
  • Peer Reviewed / Open Access
• [Journal Article] Identification and characterization of a novel <i>adenomatous polyposis coli</i> mutation in adult pancreatoblastoma (2018)
  • Author(s): Yamaguchi S, Fujii T, Izumi Y, Fukumura Y, Han M, Yamaguchi H, Akita T, Yamashita C, Kato S, Sekiya T.
  • Journal Title: Oncotarget Volume: 9(12) Issue: 12 Pages: 10818-10827
  • DOI: 10.18632/oncotarget.24017
  • Peer Reviewed / Open Access
• [Journal Article] Radiotherapy increases plasma levels of tumoral cell-free DNA in non-small cell lung cancer patients. (2018)
  • Author(s): Kageyama S, Nihei K, Karasawa K,, Sawada T, Koizumi F, Yamaguchi S, Kato S, Hojo H, Motegi A, Tsuchihara K, Akimoto T.
  • Journal Title: Oncotarget Volume: 10;9(27) Issue: 27 Pages: 19368-19378
  • DOI: 10.18632/oncotarget.25053
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular and clinical features of the TP53 signature gene expression profile in early-stage breast cancer. (2018)
  • Author(s): Yamaguchi S, Takahashi S, Mogushi K, Izumi Y, Nozaki Y, Nomizu T, Kakugawa Y, Ishida T, Ohuchi N, Ishioka C, Kato S.
  • Journal Title: Oncotarget Volume: 9 Pages: 14193-14206
  • Peer Reviewed / Open Access