Identification of novel biomarkers predicting lymph node and liver metastases colorectal cancer with CAGE analysis

• Project/Area Number: 25462068
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Juntendo University
• Principal Investigator: OKUZAWA Atsushi 順天堂大学, 医学部, 准教授 (00348913)
• Co-Investigator(Kenkyū-buntansha): KOMIYAMA HIROMITSU 順天堂大学, 医学部, 講師 (30348982) ; KAWAI JUN (独)理化学研究所, プロジェクトディレクター (30391923)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: CAGE法 / 大腸癌 / 次世代シークエンサー / 腫瘍マーカー / 肝転移 / リンパ節転移 / 網羅的発現解析 / 転移予測 / 大腸がん

Outline of Final Research Achievements

With the cap analysis of gene expression (CAGE), we conducted an exhaustive gene expression analysis in carcinoma tissue of colorectal cancer accompanied by metastases. Between the cases with and without liver metastasis or lymph node metastasis, there were differences in genes of which expression were promoted or suppressed. Some gene expressions were enhanced only in cases with liver metastasis or in those of lymph node, specifically. As a novel biomarker, the clinical application of genes identified in this work will enable us to detect earlier and to predict lymph node and liver metastases in colorectal cancer. It should help to promote clinical diagnosis and medical care of the cancer.

Research Products

• [Journal Article] Impact of chromosome 17q deletion in the primary lesion of colorectal cancer on liver metastasis (2016)
  • Author(s): KAWAI M, KOMIYAMA H, HOSOYA M, OKUBO H, FUJII T, YOKOYAMA N, SATO C, UEYAMA T, OKUZAWA A, GOTO M, KOJIMA Y, MAKOTO TAKAHASHI, KIICHI SUGIMOTO, SHUN ISHIYAMA, SHINYA MUNAKATA, OGURA D, ISHIYAMA S, NIWA I, TOMIKI Y, OCHIAI T, SAKAMOTO K
  • Journal Title: ONCOLOGY LETTERS （In press) Volume: 11 Pages: 00-00
  • Peer Reviewed / Open Access
• [Journal Article] Proposal of new classification for Stage III colon cancer based on the lymph node ratio: Analysis of 4172 patients from multi-institutional database in Japan (2015)
  • Author(s): Sugimoto K, Sakamoto K, Tomiki Y, Goto M, Kotake K, Sugihara K
  • Journal Title: Ann Surg Oncol Volume: 22(2) Pages: 528-534
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of Plasmin Protects Against Colitis in Mice by Suppressing Matrix Metalloproteinase 9-Mediated Cytokine Release From Myeloid Cells. (2015)
  • Author(s): Munakata S, Tashiro Y, Nishida C, Sato A, Komiyama H, Shimazu H, Dhahri D, Salama Y, Eiamboonsert S, Takeda K, Yagita H, Tsuda Y, Okada Y, Nakauchi H, Sakamoto K, Heissig B, Hattori K.
  • Journal Title: Gastroenterology Volume: 148 Issue: 3 Pages: 565-78
  • DOI: 10.1053/j.gastro.2014.12.001
  • Peer Reviewed / Open Access
• [Journal Article] Investigation of free cancer cells in peripheral blood using CEA mRNA expression in perioperative colorectal cancer patients. (2013)
  • Author(s): Nagayasu K, Komiyama H, Ishiyama S, Ogura D, Takahashi R, Tashiro Y, Niwa K, Sugimoto K, Kojima Y, Goto M, Tomiki Y, Niwa S, Sakamoto K.
  • Journal Title: Molecular and clinical oncology Volume: 1 Issue: 4 Pages: 668-674
  • DOI: 10.3892/mco.2013.109
  • Peer Reviewed
• [Journal Article] The validity of predicting prognosis by lymph node ratio in node-positive colon cancer. (2013)
  • Author(s): Sugimoto K, Sakamoto K, Tomiki Y, Goto M, Kojima Y, Komiyama H
  • Journal Title: Dig Surg Volume: 30 Pages: 368-374
  • Peer Reviewed
• [Presentation] Polymeric CTC-chipを用いた大腸癌CTCの検出 (2016)
  • Author(s): 呉 一眞, 細谷 理樹, 塚本 亮一, 伊藤 慎吾, 本庄 薫平, 岡澤 裕, 水越 幸輔, 宗像 慎也, 石山 隼, 杉本 起一, 神山 博彦, 小見山 博光, 高橋 玄, 柳沼 行宏, 小島 豊, 五藤 倫敏, 奥澤 淳司, 冨木 裕一, 坂本 一博, 大永 崇
  • Organizer: 第116回日本外科学会定期学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2016-04-14
• [Presentation] Patient-derived colon carcinoma cells disseminate into distant organs in various different fashions (2015)
  • Author(s): Okazawa Y, Mizukoshi K, Komiyama H, Fujii T, Goto M, Hino O, Sakamoto K, Akira Orimo A.
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] CHFR methylation is An Independent Prognostic Marker of Poor Prognosis in Gastric Cancer (2015)
  • Author(s): Sugimoto K, Humbert A, Lu Z, Chen C, Rodgers K, Lee,B Griffin C, Sato K, Orita H, Ito T, Komiyama H, Kojima Y, Goto M, Tomiki Y, Sakamoto K, Brock M
  • Organizer: 2015 American Association for Cancer Research Annual Meeting
  • Place of Presentation: PennsylvaniaUSA
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] PAI-1阻害剤による血管新生及び組織再生促進療法 (2013)
  • Author(s): 3. 宗像慎也，田代良彦，島津 浩，西田知恵美，イスマエルグリツリ，佐藤亜紀，小泉麻季子，楠畑かおり，小見山博光，坂本一博，宮田敏男，ハイジッヒベアテ，服部浩一
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡
• [Presentation] The development of gross hepatic and pulmonary metastases in a patient-derived colorectal tumor xenograft model. (2013)
  • Author(s): 2. Kosuke Mizukoshi，Yu Okazawa，Hiromitsu Komiyama，Tomoaki Fujii，Yasuhiko Ito， Michitoshi Goto，Sonoko Habu，Okio Hino，Kazuhiro Sakamoto and Akira Orimo
  • Organizer: 患者大腸癌組織片の移植モデルにおける顕著な肝臓および肺への転移形成
  • Place of Presentation: 横浜
• [Presentation] CGHによる大腸がん原発巣ゲノム変異と肝転移および予後に関する検討 (2013)
  • Author(s): 28. 河合雅也，小見山博光，髙橋里奈，杉本起一，神山博彦, 小島 豊，五藤倫敏，奥澤淳司，冨木裕一，坂本一博
  • Organizer: 第68回日本消化器外科学会
  • Place of Presentation: 宮崎
• [Presentation] 大腸癌における染色体異常を指標とした肝転移と予後の比較解析 (2013)
  • Author(s): 31. 杉本起一，河合雅也，小見山博光，市川亮介，本庄薫平，呉 一眞，盧 尚志，伊藤慎吾， 細谷理樹，藤井智明，大久保はるな，柳沼行宏，奥澤淳司，冨木裕一，坂本一博
  • Organizer: 第24回日本消化器癌発生学会
  • Place of Presentation: 金沢市
• [Remarks] 順天堂大学 下部消化管外科
  • URL: http://www.juntendo.ac.jp/graduate/laboratory/labo/kabusyoukakan/
• [Remarks] 順天堂大学 下部消化管外科
  • URL: http://www.juntendo.ac.jp/hospital/clinic/daicho/
• [Patent(Industrial Property Rights)] 大腸がんの転移又は再発リスクの評価方法 (2014)
  • Inventor(s): 小見山博光，坂本一博，奥澤淳司，塩大津敬，林崎良英，川路 英哉
  • Industrial Property Rights Holder: 小見山博光，坂本一博，奥澤淳司，塩大津敬，林崎良英，川路 英哉
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-01-31