Establish the early diagnosis of esophageal cancer using SNP array and ctDNA sequencing.

• Project/Area Number: 18K15323
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kagoshima University (2019-2021); Kyushu University (2018)
• Principal Investigator: Tsuruda Yusuke 鹿児島大学, 鹿児島大学病院, 医員 (70812767)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 放射線化学療法 / 治療抵抗性 / 治療感受性 / デコンボルーション / CAF / CRT / immunodecovolution / B細胞 / 液性免疫 / ｌiquid biospy ctDNA / 早期診断 / 食道がん / 発がんハイリスク / liquid biospy / ctDNA / 遺伝子多型 / バーコードシークエンス / リキッドバイオプシー / 食道癌

Outline of Final Research Achievements

Prior to building just an early diagnosis of esophageal cancer, we aimed to establish the feasible measure to improve the clinical outcome of the postoperative esophageal cancer cases. We scrutinized a biomarker to identify the resistant cases to the CRT treatment immediately against esophageal cancer cases and conducted RNA Seq in pretreatment primary tumors from 16 sensitive cases and those from 17 resistance cases at first. Consequently, the CRT-resistant issues indicated an abundant expression of CAF (Cancer-associated fibroblast) score than the CRT-sensitive cases with a statistical significance. Therefore, we will discover the CRT-resistant marker related to the malignant CAF accumulation and apply it to the liquid biopsy assay for clinical diagnosis.

Academic Significance and Societal Importance of the Research Achievements

本研究成果によりCRT抵抗性に関わるがん微小環境側における制御機構を解明できる。すなわち多様性に富む癌細胞に対して、がん微小環境における変異は普遍的に制御できる可能性が高く、臨床的に有意義である。また、放射線治療は局所療法のなかでも低侵襲であり様々な癌腫で用いられている。本解析の結果得られるCAFを制御する分子は食道がん以外でも有用な可能性があり、社会的意義は大きい。

Research Products

• [Journal Article] KIF15 Expression in Tumor-associated Monocytes Is a Prognostic Biomarker in Hepatocellular Carcinoma. (2020)
  • Author(s): Kitagawa A, Masuda T, Takahashi J, Tobo T, Noda M, Kuroda Y, Hu Q, Kouyama Y, Kobayashi Y, Kuramitsu S, Sato K, Fujii A, Yoshikawa Y, Wakiyama H, Shimizu D, Tsuruda Y, Eguchi H, Doki Y, Mori M, Mimori K.
  • Journal Title: Cancer Genomics Proteomics. Volume: 17(2) Issue: 2 Pages: 141-149
  • DOI: 10.21873/cgp.20174
  • Peer Reviewed / Open Access
• [Journal Article] Drug repositioning in cancer: The current situation in Japan. (2020)
  • Author(s): Masuda T, Tsuruda Y, Matsumoto Y, Uchida H, Nakayama KI, Mimori K.
  • Journal Title: Cancer Sci. Volume: 111(4) Issue: 4 Pages: 1039-1046
  • DOI: 10.1111/cas.14318
  • Peer Reviewed / Open Access
• [Journal Article] N-Cadherin mRNA Levels in Peripheral Blood Could Be a Potential Indicator of New Metastases in Breast Cancer: A Pilot Study. (2020)
  • Author(s): Masuda T, Ueo H, Kai Y, Noda M, Hu Q, Sato K, Fujii A, Hayashi N, Tsuruda Y, Otsu H, Kuroda Y, Eguchi H, Ohno S, Mimori K, Ueo H.
  • Journal Title: Int J Mol Sci. Volume: - Issue: 2 Pages: 511-511
  • DOI: 10.3390/ijms21020511
  • Peer Reviewed / Open Access
• [Journal Article] Oncogenic splicing abnormalities induced by DEAD-Box Helicase 56 amplification in colorectal cancer. (2019)
  • Author(s): Kouyama Y, Masuda T, Fujii A, Ogawa Y, Sato K, Tobo T, Wakiyama H, Yoshikawa Y, Noda M, Tsuruda Y, Kuroda Y, Eguchi H, Ishida F, Kudo SE, Mimori K.
  • Journal Title: Cancer Sci. Volume: 110(10) Issue: 10 Pages: 3132-3144
  • DOI: 10.1111/cas.14163
  • Peer Reviewed / Open Access
• [Journal Article] A clinical trial of somatic and germline analyses for healthy longevity in a postoperative cancer patient. (2019)
  • Author(s): Hayashi N, Kuroda Y, Saito T, Tsuruda Y, Niida A, Otsu H, Eguchi H, Masuda T, Suzuki Y, Natsugoe S, Mimori K.
  • Journal Title: Surg Today. Volume: Epub Issue: 9 Pages: 738-747
  • DOI: 10.1007/s00595-019-01789-7
  • Peer Reviewed / Open Access
• [Journal Article] CRMP5-associated GTPase (CRAG) Is a Candidate Driver Gene for Colorectal Cancer Carcinogenesis. (2019)
  • Author(s): Shimizu D, Masuda T, Sato K, Tsuruda Y, Otsu H, Kuroda Y, Eguchi H, Kodera Y, Mimori K.
  • Journal Title: Anticancer Res. Volume: 39(1) Issue: 1 Pages: 99-106
  • DOI: 10.21873/anticanres.13084
  • Peer Reviewed / Open Access
• [Journal Article] Three-stage laparoscopic surgery in a morbidly obese patient with Hinchey III diverticulitis: a case report. (2019)
  • Author(s): Tanaka T, Kita Y, Mori S, Baba K, Tanabe K, Wada M, Tsuruda Y, Tanoue K, Yanagita S, Maemura K, Natsugoe S.
  • Journal Title: Surg Case Rep. Volume: 5 Issue: 1 Pages: 24-24
  • DOI: 10.1186/s40792-019-0588-7
  • Peer Reviewed / Open Access
• [Journal Article] Circulating Pre-microRNA-488 in Peripheral Blood Is a Potential Biomarker for Predicting Recurrence in Breast Cancer. (2018)
  • Author(s): Masuda T, Shinden Y, Noda M, Ueo H, Hu Q, Yoshikawa Y, Tsuruda Y, Kuroda Y, Ito S, Eguchi H, Ohno S, Mimori K.
  • Journal Title: Anticancer Res. Volume: 38(8) Issue: 8 Pages: 4515-4523
  • DOI: 10.21873/anticanres.12755
  • Peer Reviewed / Open Access
• [Journal Article] Laparoscopic cholecystectomy with aberrant bile duct detected by intraoperative fluorescent cholangiography concomitant with angiography: A case report. (2018)
  • Author(s): Tsuruda Y, Okumura H, Setoyama T, Hiwatashi K, Minami K, Ando K, Wada M, Maenohara S, Natsugoe S.
  • Journal Title: Int J Surg Case Rep. Volume: 51 Pages: 14-16
  • DOI: 10.1016/j.ijscr.2018.08.009
  • Peer Reviewed / Open Access
• [Presentation] 末梢血中pre-miR-488発現の胃癌予後予測因子としての有用性． (2019)
  • Author(s): 鶴田祐介，増田隆明，野田美和，清水大，吉川幸宏，倉光正太郎，藤井昌志，北川彰洋，高橋純一，大津甫，黒田陽介，江口英利，夏越祥次，三森功士
  • Organizer: 第119回日本外科学会定期学術集会
• [Presentation] 切除不能胃癌・大腸癌の化学療法症例における増悪様式別の予後検討. (2019)
  • Author(s): 鶴田祐介，増田隆明，倉光正太郎，北川彰洋，藤井昌志，大津甫，黒田陽介，江口英利，夏越祥次，三森功士
  • Organizer: 第74回日本消化器外科学会総会
• [Presentation] 大腸がん肝転移再発の機序の理解と早期診断の実現にむけて． (2019)
  • Author(s): 鶴田祐介，崎村正太郎，長山聡，増田隆明，柴田龍弘，三森功士
  • Organizer: 第28回日本がん転移学会学術集会・総会
• [Presentation] 胃癌の予後予測因子としての血中pre-miR-488の同定． (2019)
  • Author(s): 鶴田祐介，増田隆明，深川剛生，野田美和，清水大，吉川幸宏，伊藤修平，胡慶江, 松本佳大，大津甫，内田博喜，夏越祥次，三森功士
  • Organizer: 第78回 日本癌学会学術総会．
  • Int'l Joint Research
• [Presentation] 腹腔鏡補助下脾臓摘出術を施行した脾原発悪性リンパ腫の一例． (2019)
  • Author(s): 鶴田祐介，松本佳大，大津甫，内田博喜，増田隆明，三森功士
  • Organizer: 第32回日本内視鏡外科学会総会．
• [Presentation] weekly パクリタキセル＋ベバシズマブ療法中に腋窩動脈出血を来たした再発乳癌の1例． (2019)
  • Author(s): 鶴田祐介，増田隆明，林直樹，野田美和，大津甫，黒田陽介，江口英利，田中文明，夏越祥次，三森功士
  • Organizer: 第41回日本癌局所療法研究会
• [Presentation] SATB1 is a novel prognostic factor in esophageal cancer patients and promotes migration and invasion of esophageal cancer (2018)
  • Author(s): Y Tsuruda, R Kogo, S Ito, A Kitagawa, A Fujii, S Kuramitsu, D Shimizu, Y Kuroda, H Eguchi, T Masuda, S Natsugoe, M Mori, K Mimori.
  • Organizer: AACR Annual Meeting 2018
  • Int'l Joint Research
• [Presentation] 7番染色体短腕（7p）に存在する大腸癌の新規ドライバー遺伝子DDX56の同定 (2018)
  • Author(s): 鶴田祐介、神山勇太、増田隆明、小川悠史、佐藤晋彰、胡慶江、野田美和、吉川幸宏、北川彰洋、藤井昌志、倉光正太郎、清水大、伊藤修平、江口英利、黒田陽介、三森功士
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] 食道扁平上皮癌におけるSATB1発現の意義 (2018)
  • Author(s): 鶴田祐介、伊藤修平、吉川幸宏、清水大、倉光正太郎、黒田陽介、江口英利、増田隆明、夏越祥次、三森功士
  • Organizer: 第73回日本消化器外科学会総会
• [Presentation] 胃癌における血中pre-miR-488の予後予測因子としての有用性 (2018)
  • Author(s): 鶴田祐介、増田隆明、野田美和、倉光正太郎、脇山浩明、清水大、吉川幸宏、大津甫、黒田陽介、江口英利、夏越祥次、三森功士
  • Organizer: 第77回日本癌学会学術総会
  • Int'l Joint Research