Identification of lung metastasis predictive marker for colorectal cancer with gene explession analysis using CAGE

• Project/Area Number: 18K08798
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Juntendo University
• Principal Investigator: Yaginuma Yukihiro 順天堂大学, 医学部, 非常勤講師 (60338415)
• Co-Investigator(Kenkyū-buntansha): 小見山 博光 順天堂大学, 医学部, 非常勤講師 (30348982) ; 茂櫛 薫 順天堂大学, 大学院医学研究科, 非常勤講師 (60569292)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 大腸癌 / 肺転移 / 転移マーカー / 腫瘍マーカー / 採血 / 再発予測マーカー / 大腸がん / 転移予測マーカー / CAGE法 / CAGE / マーカー

Outline of Final Research Achievements

This study aims to develop a predictive marker for lung metastasis of colorectal cancer in blood samples. We found a set of genes that show differential expression between cases with and without metastases. We analyzed the gene expression in blood samples and compared the results in preoperative, postoperative, and recurrence blood samples drawn from each patient. Among the genes detected in the preoperative blood samples but not in the postoperative samples, we have already identified some genes with mutations that were elevated in samples with postoperative recurrence. Further investigation is needed to verify the usefulness of these candidates as recurrent and predictive marker for lung metastasis of the colorectal cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究では採血検体，癌部，正常部から大腸癌の肺転移を予測する肺転移予測マーカーを取得する. 本研究が新規開発する大腸癌肺転移予測マーカーは，現状では評価できない肺転移リスク，また検出できない初期の肺転移を，採血から診断可能にし、患者ごとの治療選択と予後改善を目指す. 大腸癌患者の採血や術前内視鏡生検から容易に肺転移を予測，初期検出できるようになれば，手術や術前化学療法の適応にも大きな影響を及ぼすことが予想される．さらに既存のstage分類の再考，新たな分類の構築が可能となるなど，がん医療に革新をもたらす．

Research Products

• [Journal Article] Usefulness of an IL-6 Semi-Quantification Kit in Patients with Perforative Peritonitis (2021)
  • Author(s): Ichikawa R, Sugimoto K, Kure K, Honjo K, Takahashi R, Okazawa Y, Kawai M, Munakata S,Komiyama H, Sakamoto K et al..
  • Journal Title: Juntendo Medical Journal Volume: 67 Issue: 2 Pages: 158-164
  • DOI: 10.14789/jmj.2021.67.JMJ20-OA09
  • NAID: 130008032136
  • ISSN: 2187-9737, 2188-2126
  • Peer Reviewed / Open Access
• [Journal Article] Identification of MicroRNA 15b-3p as a Diagnostic Marker for Early Stage of Colorectal Cancer Through Comprehensive RNA Analysis (2021)
  • Author(s): Tsukamoto R, Hosoya M, Fukaya M, Yokoyama N, Kawano S, Sugimoto K, Takahashi M, Sakamoto K, Komiyama H,
  • Journal Title: Juntendo Medical Journal Volume: 67 Issue: 3 Pages: 272-281
  • DOI: 10.14789/jmj.JMJ20-OA12
  • NAID: 130008059636
  • ISSN: 2187-9737, 2188-2126
  • Peer Reviewed / Open Access
• [Journal Article] Antitumor effects of novel mAbs against cationic amino acid transporter 1 (CAT1) on human CRC with amplified CAT1 gene (2021)
  • Author(s): Okita K, Hara Y, Okura H, Hayashi H, Sasaki Y, Masuko S, Kitadai E, Masuko K, Yoshimoto S, Komiyama H, Sakamoto K, Masuko T.et al
  • Journal Title: Cancer Sci Volume: 112 Pages: 563-574
  • Peer Reviewed / Open Access
• [Journal Article] Using the polymeric circulating tumor cell chip to capture circulating tumor cells in blood samples of patients with colorectal cancer (2020)
  • Author(s): Kure K, Hosoya M, Ueyama T, Fukaya M, Sugimoto K, Tomiki Y,Ohnaga T, Sakamoto K, Komiyama H.
  • Journal Title: Oncl Lett Volume: 19 Pages: 2286-2294
  • DOI: 10.3892/ol.2020.11335
  • Peer Reviewed / Open Access
• [Journal Article] Angiopoietin-2 as a prognostic factor in patients with incurable stage IV colorectal cancer. (2020)
  • Author(s): Munakata S, Ueyama T, Ishihara H, Komiyama H, Tsukamoto R, Kawai M, Takahashi M, Kojima Y, Tomiki Y,
  • Journal Title: J Gastrointest Cancer. Volume: 2020 Online ahead of print Issue: 1 Pages: 000-000
  • DOI: 10.1007/s12029-020-00392-1
  • Peer Reviewed / Open Access
• [Journal Article] Metastatic seeding of human colon cancer cell clusters expressing the hybrid epithelial/mesenchymal state. (2019)
  • Author(s): Mizukoshi K, Okazawa Y, Haeno H, Koyama Y, Sulidan K, Komiyama H, Saeki H, Ohtsuji N, Ito Y, Kojima Y, Goto M, Habu S, Hino O, Sakamoto K, Orimo A.
  • Journal Title: Int J Cancer Volume: 146 Issue: 9 Pages: 2547-2562
  • DOI: 10.1002/ijc.32672
  • Peer Reviewed / Open Access
• [Journal Article] Stromal fibroblasts induce metastatic tumor cell clusters via epithelial-mesenchymal plasticity. (2019)
  • Author(s): Matsumura Y, Ito Y, Mezawa Y, Sulidan K, Daigo Y, Hiraga T, Mogushi K, Wali N, Suzuki H, Itoh T, Miyagi Y, Yokose T, Shimizu S, Takano A, Terao Y, Saeki H, Ozawa M, Abe M, Takeda S, Okumura K, Habu S, Hino O, Takeda K, Hamada M, Orimo A.
  • Journal Title: Life Sci Alliance Volume: 2(4):e201900425. Issue: 4 Pages: 1-24
  • DOI: 10.26508/lsa.201900425
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Estrogen receptor-positive ductal carcinoma in situ frequently overexpresses HER2 protein without gene amplification. (2019)
  • Author(s): Horimoto Y, Terao T, Tsutsumi Y, Tanabe M, Mogushi K, Hlaing MT, Sasaki R, Saeki H, Okazaki M, Sonoue H, Arakawa A, Saito M.
  • Journal Title: Am J Surg Pathol Volume: 43(9) Issue: 9 Pages: 1221-1228
  • DOI: 10.1097/pas.0000000000001300
  • Peer Reviewed / Open Access
• [Journal Article] Mitochondrial ribosomal protein PTCD3 mutations cause oxidative phosphorylation defects with Leigh syndrome. (2019)
  • Author(s): Borna NN, Kishita Y, Kohda M, Lim SC, Shimura M, Wu Y, Mogushi K, Yatsuka Y, Harashima H, Hisatomi Y, Fushimi T, Ichimoto K, Murayama K, Ohtake A, Okazaki Y.
  • Journal Title: Neurogenetics Volume: 20(1) Issue: 1 Pages: 9-25
  • DOI: 10.1007/s10048-018-0561-9
  • Peer Reviewed
• [Journal Article] Comprehensive molecular characterization of liver cancer and inheritance of the phenotypic traits during tumor recurrence. (2019)
  • Author(s): Shimada S, Mogushi K, Akiyama Y, Furuyama T, Watanabe S, Ogura T, Ogawa K, Ono H, Mitsunori Y, Ban D, Kudo A, Arii S, Tanabe M, Wands JR, Tanaka S.
  • Journal Title: EBioMedicine Volume: 40 Pages: 457-470
  • DOI: 10.1016/j.ebiom.2018.12.058
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of genes and pathways, including the CXCL2 axis, altered by DNA methylation in hepatocellular carcinoma. (2019)
  • Author(s): Subat S, Mogushi K, Yasen M, Kohda T, Ishikawa Y, Tanaka H.
  • Journal Title: Journal of cancer research and clinical oncology Volume: 145(3) Issue: 3 Pages: 675-684
  • DOI: 10.1007/s00432-018-2824-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Pharmacological targeting of neutrophil serine proteases prevents lethality in dextran sulfate sodium (DSS)-induced colitis in mice (2018)
  • Author(s): Ro H, Munakata S, Ueyama T, Komiyama H, Takahashi M, Kojima Y, Tomiki Y, Sakamoto K
  • Journal Title: Journal of Gastrointestinal & Digestive System Volume: 8 Issue: 01 Pages: 551-551
  • DOI: 10.4172/2161-069x.1000551
  • Peer Reviewed / Open Access
• [Journal Article] High-sensitivity detection of micrometastases generated by GFP lentivirus-transduced organoids cultured from a patient-derived colon tumor. (2018)
  • Author(s): OkazawaY, Mizukoshi K, KoyamaY, Okubo S, Komiyama H, Kojima Y, Goto M, Habu S, Hino O, Sakamoto K, Orimo A.
  • Journal Title: J Vis Exp Volume: 136(e57374) Issue: 136 Pages: 463-473
  • DOI: 10.3791/57374
  • Peer Reviewed / Open Access
• [Journal Article] COQ2 variants in Parkinson's disease and multiple system atrophy. (2018)
  • Author(s): Mikasa M, Kanai K, Li Y, Yoshino H, Mogushi K, Hayashida A, Ikeda A, Kawajiri S, Okuma Y, Kashihara K, Sato T, Kondo H, Funayama M, Nishioka K, Hattori N.
  • Journal Title: J Neural Transm (Vienna) Volume: - Issue: 6 Pages: 938-944
  • DOI: 10.1007/s00702-018-1885-1
  • Peer Reviewed / Open Access
• [Journal Article] Elucidation of inhibitory effects on metastatic sentinel lymph nodes of breast cancer during One-Step Nucleic Acid Amplification. (2018)
  • Author(s): Horimoto Y, Tanabe M, Kazuno S, Miura Y, Mogushi K, Sonoue H, Arakawa A, Kajino K, Kobayashi T, Saito M.
  • Journal Title: Sci Rep Volume: 8(1):7563 Issue: 1 Pages: 1-7
  • DOI: 10.1038/s41598-018-25911-w
  • Peer Reviewed / Open Access
• [Journal Article] Fatty Acid Binding Protein 4 (FABP4) Overexpression in Intratumoral Hepatic Stellate Cells within Hepatocellular Carcinoma with Metabolic Risk Factors (2018)
  • Author(s): Chiyonobu Norimichi、Shimada Shu、Akiyama Yoshimitsu、Mogushi Kaoru、Itoh Michiko、Akahoshi Keiichi、Matsumura Satoshi、Ogawa Kosuke、Ono Hiroaki、Mitsunori Yusuke、Ban Daisuke、Kudo Atsushi、Arii Shigeki、Suganami Takayoshi、Yamaoka Shoji、Ogawa Yoshihiro、Tanabe Minoru、Tanaka Shinji
  • Journal Title: Am. J. Pathol. Volume: 188 Issue: 5 Pages: 1213-1224
  • DOI: 10.1016/j.ajpath.2018.01.012
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Non-small cell lung carcinoma with diffuse co-expression of thyroid transcription factor-1 and ΔNp63/p40 (2018)
  • Author(s): Hayashi Takuo、Takamochi Kazuya、Yanai Yuka、Mitani Keiko、Tomita Hisashi、Mogushi Kaoru、Suehara Yoshiyuki、Takahashi Fumiyuki、Suzuki Kenji、Saito Tsuyoshi、Yao Takashi
  • Journal Title: Human Pathology Volume: S0046-8177 Pages: 30037-6
  • DOI: 10.1016/j.humpath.2018.01.023
  • Peer Reviewed / Open Access
• [Journal Article] Tumor sidedness and enriched gene groups for efficacy of first-line cetuximab treatment in metastatic colorectal cancer. (2018)
  • Author(s): Sunakawa Y, Mogushi K, Lenz HJ, Zhang W, Tsuji A, Takahashi T, Denda T, Shimada K, Kochi M, Nakamura M, Kotaka M, Ichikawa W. et al
  • Journal Title: Molecular Cancer Therapeutics Volume: 17(12) Pages: 2788-2795
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tumor suppressor functions of DAXX through histone H3.3/H3K9me3 pathway in pancreatic NETs. (2018)
  • Author(s): Ueda H, Akiyama Y, Shimada S, Mogushi K, Serizawa M, Matsumura S, Mitsunori Y, Aihara A, Ban D, Ochiai T, Kudo A, Tanabe M, Tanaka S.
  • Journal Title: Endocr Relat Cancer Volume: 25(6) Issue: 6 Pages: 619-631
  • DOI: 10.1530/erc-17-0328
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] KCTD12 is negatively regulated by Kit in gastrointestinal stromal tumors. (2018)
  • Author(s): Suehara Y, Akaike K, Mukaihara K, Kurisaki-Arakawa A, Kubota D, Okubo T, Mitomi H, Mitani K, Takahashi M, Toda-Ishii M1, Kim Y, Tanabe Y, Takagi T, Hayashi T, Mogushi K, Kaneko K, Yao T, Saito T.
  • Journal Title: Oncotarget Volume: 9(43) Issue: 43 Pages: 27016-27026
  • DOI: 10.18632/oncotarget.25469
  • Peer Reviewed / Open Access
• [Journal Article] GCH1 mutations in dopa-responsive dystonia and Parkinson's disease. (2018)
  • Author(s): Yoshino H, Nishioka K, Li Y, Oji Y, Oyama G, Hatano T, Machida Y, Shimo Y, Hayashida A, Ikeda A, Mogushi K, Shibagaki Y, Hosaka A, Iwanaga H, Fujitake J, Ohi T, Miyazaki D, Sekijima Y, Oki M, Kusaka H, Fujimoto KI Ugawa Y, Funayama M, Hattori N.
  • Journal Title: Journal of Neurology Volume: 265(8) Issue: 8 Pages: 1860-1870
  • DOI: 10.1007/s00415-018-8930-8
  • Peer Reviewed / Open Access
• [Journal Article] Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review. (2018)
  • Author(s): Watanabe J, Togo S, Sumiyoshi I, Namba Y, Suina K, Mizuno T, Kadoya K, Motomura H, Iwai M, Nagaoka T, Sasaki S, Hayashi T, Uekusa T, Abe K, Urata Y, Sakurai F, Mizuguchi H, Kato S, Takahashi K.
  • Journal Title: Oncotarget Volume: 9(35) Issue: 35 Pages: 24000-24013
  • DOI: 10.18632/oncotarget.25257
  • Peer Reviewed / Open Access
• [Journal Article] Correction: Radiotherapy increases plasma levels of tumoral cell-free DNA in non-small cell lung cancer patients. (2018)
  • Author(s): Kageyama SI, Nihei K, Karasawa K, Sawada T, Koizumi F, Yamaguchi S, Kato S, Hojo H, Motegi A, Tsuchihara K, Akimoto T.
  • Journal Title: Oncotarget Volume: 9(34) Issue: 34 Pages: 23844-23844
  • DOI: 10.18632/oncotarget.25378
  • Peer Reviewed / Open Access
• [Journal Article] Intermittent Withdrawal of Oxaliplatin for Alleviating Neurotoxicity during Oxaliplatin-Based Chemotherapy for Japanese Patients with Inoperable or Metastatic Colorectal Cancer: A Phase 2 Multicenter Study (2018)
  • Author(s): Kato S, Imai H, Gamoh M, Takahata T, Ohori H, Yasuda K, Niitani T, Murakawa Y, Amagai K, Isobe H, Shindo Y, Kuroki M, Sakamoto Y, Shimodaira H, Yoshioka T, Ishioka C.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 245 Issue: 1 Pages: 21-28
  • DOI: 10.1620/tjem.245.21
  • NAID: 130006733224
  • ISSN: 0040-8727, 1349-3329
  • 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] 四次治療のトラベクテジン投与にて長期の無増悪生存期間が得られている平滑筋肉腫再発の1症例 (2018)
  • Author(s): 野崎 由美, 山口 茂夫, 高木 辰哉, 加藤 俊介
  • Journal Title: 癌と化学療法 Volume: 46巻2号 Pages: 275-277
  • Peer Reviewed
• [Presentation] 当院での鼠径ヘルニア対するロボット支援下TAPP法の導入と展望 (2022)
  • Author(s): 塚本亮一・河口 恵・呉 一眞・岡澤 裕・髙橋里奈・ 柳沼行宏・小島 豊・福永 哲 坂本一博
  • Organizer: 第20回日本ヘルニア学会学術集会
• [Presentation] 網羅的解析を用いた新規結腸癌診断マーカーの探索. (2019)
  • Author(s): 塚本亮一, 小見山博光, 河野眞吾, 河合雅也, 高橋玄, 小島豊, 冨木裕一, 坂本一博
  • Organizer: 第57回日本癌治療学会学術集会, 福岡.
• [Presentation] 患者大腸癌細胞集団の中間型上皮間葉移行を介した浸潤・転移機構. (2019)
  • Author(s): 水越幸輔，岡澤 裕，波江野 洋，小山 侑，大久保捷奇，Kaidiliavi Sulidan，伊藤恭彦，小見山博光，杉本起一，小島 豊，五藤倫敏，垣生園子，樋野興夫，折茂 彰，坂本一博
  • Organizer: 第30回日本消化器癌発生学会総会，横浜.
• [Remarks] 順天堂大学下部消化管外科学(消化器外科学講座)
  • URL: https://www.juntendo.ac.jp/graduate/laboratory/labo/kabusyoukakan/
• [Remarks] 順天堂大学下部消化管外科学（消化器外科学講座）
  • URL: https://www.juntendo.ac.jp/graduate/laboratory/labo/kabusyoukakan/
• [Remarks] 順天堂大学大学院 下部消化管外科学
  • URL: https://www.juntendo.ac.jp/graduate/laboratory/labo/kabusyoukakan/
• [Remarks] 順天堂大学大学院 下部消化管外科学
  • URL: https://www.juntendo.ac.jp/graduate/laboratory/labo/kabusyoukakan/