The novel markers to predict the sensitivity to chemotherapy in ESCC and GC

• Project/Area Number: 24591949
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: SAITO seiya 熊本大学, 医学部附属病院, 非常勤診療医師 (00594475)
• Co-Investigator(Kenkyū-buntansha): HAYASHI Naoko 熊本大学, 医学部附属病院, 非常勤診療医師 (20452899) ; BABA Yoshifumi 熊本大学, 大学院生命科学研究部, 講師 (20599708) ; IWATSUKI Masaaki 熊本大学, 医学部附属病院, 非常勤診療医師 (50452777)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: microRNA 2 / RPN2 / chemo-resistance / PTEN / FBXW7 / microRNA / 食道扁平上皮癌 / 胃癌 / DCF療法 / Herceptin / 個別化治療 / 術前化学療法 / 生検組織

Outline of Final Research Achievements

We revealed that RPN2 expression in biopsy specimens could be a useful predictive marker for docetaxel-based neoadjuvant chemotherapy in ESCC. However, RPN2 expression is not associated microRNA expression. And therefore, we would reveal the relationship between Herceptin resistance and microRNA expression in gastric cancer. We revealed that the miR-21/PTEN pathway regulated the sensitivity of HER2-positive GC cell lines to trastuzumab through modulation apoptosis. Furthermore, we revealed the miR-223/FBXW7 pathway regulates the sensitivity of a HER2-positive GC cell line to trastuzumab through the modulation of apoptosis. We disclosed the miR-21/PTEN and miR-223/FBXW7 regulated the sensitivity of HER2-positive GC cell lines to trastuzumab through modulation apoptosis. We consider that miR-21 and miR-223 expression could be a useful predictive marker for Herceptin chemotherapy in gastric cancer.

Research Products

• [Journal Article] The sensitivity of gastric cancer to trastuzumab is regulated by the miR-223/FBXW7 pathway (2015)
  • Author(s): Eto K, Iwatsuki M, Watanabe M, Ishimoto T, Ida S, Imamura Y, Iwagami S, Baba Y, Sakamoto Y, Miyamoto Y, Yoshida N, Baba H
  • Journal Title: Int J Cancer Volume: 136(7) Issue: 7 Pages: 1537-45
  • DOI: 10.1002/ijc.29168
  • Peer Reviewed
• [Journal Article] The microRNA-21/PTEN pathway regulates the sensitivity of HER2-positive gastric cancer cells to trastuzumab (2014)
  • Author(s): Eto K, Iwatsuki M, Watanabe M, Ida S, Ishimoto T, Iwagami S, Baba Y, Sakamoto Y, Miyamoto Y, Yoshida N, Baba H
  • Journal Title: Ann Surg Oncol Volume: 21(1) Issue: 1 Pages: 343-50
  • DOI: 10.1245/s10434-013-3325-7
  • Peer Reviewed
• [Journal Article] Clinical impact of serum exosomalmicroRNA-21 in human esophagealsquamous cell carcinoma, as a clinicalbiomarker (2013)
  • Author(s): Tanaka Y,Kammohara H,KinoshitaK,Kurashige J,Ishimoto T, Iwatsuki M,Watanabe M, Baba H
  • Journal Title: Cancer Volume: 119 Issue: 6 Pages: 1159-1167
  • DOI: 10.1002/cncr.27895
  • Peer Reviewed
• [Journal Article] Overexpressionitin ligase FBXW7in esopha of microRNA-223 regulatesthe ubiqu geal squamous cellcarcinoma (2012)
  • Author(s): Kurashige J, Watanabe M, Iwatsuki M,Kinoshita K, Saito S,Hiyoshi Y,Kamohara H, Baba H, Mimori K
  • Journal Title: Br J Cancer Volume: 106 Issue: 1 Pages: 182-188
  • DOI: 10.1038/bjc.2011.509
  • Peer Reviewed
• [Journal Article] Serum microRNA-21 is a novel biomarker in patients with esophageal squamous cell carcinoma (2012)
  • Author(s): Kurashige J
  • Journal Title: Journal of Surgical Oncology Volume: (印刷中) Issue: 2 Pages: 188-92
  • DOI: 10.1002/jso.23064
  • Peer Reviewed
• [Journal Article] PN2 expression predicts response todocetaxel in oesophageal squamouscell carcinoma. (2012)
  • Author(s): Kurashige J, Watanabe M, Iwatsuki M,Kinoshita K, Saito S, Nagai Y,Ishimoto T, Baba Y, Mimori K, Baba H
  • Journal Title: Br J Cancer Volume: 107 Issue: 8 Pages: 1233-8
  • DOI: 10.1038/bjc.2012.396
  • Peer Reviewed
• [Journal Article] Carcinogenesis of intraductal papillary mucinous neoplasm of the pancreas : loss of microrna-101 promotes overexpression of histone methyltransferase EZH2 (2012)
  • Author(s): Nakahara O
  • Journal Title: Annals of Surgical Oncology Volume: (印刷中) Issue: S3 Pages: 565-71
  • DOI: 10.1245/s10434-011-2068-6
  • Peer Reviewed
• [Presentation] 食道扁平上皮癌に対する術前DCF療法後切除症例における血清抗p53抗体値の意義 (2015)
  • Author(s): 日吉 幸晴
  • Organizer: 第48回制癌剤適応研究会
  • Place of Presentation: 浜松
  • Year and Date: 2015-03-20
• [Presentation] The microRNA-223/FBXW7/MCL1 pathway regulates the sensitivity of HER2-positive gastric cancer cells to Trastuzumab (2014)
  • Author(s): Eto K
  • Organizer: 9th ISCRT
  • Place of Presentation: Tokyo
  • Year and Date: 2014-10-31 – 2014-11-01
• [Presentation] 食道癌に対する術前DCF 療法の有用性と今後の展望 (2013)
  • Author(s): 渡邊雅之
  • Organizer: 第113回日本外科学会
  • Place of Presentation: 福岡国際会議場
• [Presentation] 吉田直矢 (2013)
  • Author(s): 食道癌に対するDCF併用化学放射線療法の有用性
  • Organizer: 第67回日本食道学会学術集会
  • Place of Presentation: 大阪国際会議場
• [Presentation] 食道扁平上皮癌においてmicroRNA-223は癌抑制遺伝子ユビキチンリガーゼ複合体基質ユニットFBXW7の発現を制御する (2012)
  • Author(s): 蔵重淳二
  • Organizer: 第112回日本外科学会定期学術集会
  • Place of Presentation: 幕張メッセ国際会議場 千葉
• [Presentation] Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in esophageal squamous cell carcinoma (2012)
  • Author(s): 蔵重淳二
  • Organizer: AACR Annual Meeting 2012
  • Place of Presentation: McCormick Place West（アメリカ・シカゴ）