The role of MED12 expression in molecular mechanism of drug resistance of colorectal cancer

• Project/Area Number: 15K10130
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Niigata University
• Principal Investigator: Yoshifumi Shimada 新潟大学, 医歯学系, 助教 (20706460)
• Co-Investigator(Kenkyū-buntansha): 坂田 純 新潟大学, 医歯学系, 講師 (70447605) ; 味岡 洋一 新潟大学, 医歯学系, 教授 (80222610) ; 亀山 仁史 新潟大学, 医歯学系, 准教授 (40626420) ; 小杉 伸一 新潟大学, 医歯学総合病院, 特任教授 (90401736) ; 小林 隆 新潟大学, 医歯学総合病院, 講師 (40464010)
• Co-Investigator(Renkei-kenkyūsha): WAKAI Toshifumi 新潟大学, 医歯学系, 教授 (50372470)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: MED12 / 大腸癌 / 転写メディエーター / 薬剤耐性 / 薬物療法抵抗性

Outline of Final Research Achievements

MED12 is a transcriptional mediator complex subunit, which negatively regulates transforming growth factor-β (TGF-β) pathway. TGF-β pathway plays a main role of induction signals of epithelial mesenchymal transition (EMT). We aimed to investigate the clinical significance of MED12 expression in patients with colorectal cancer (CRC). A total of 100 patients diagnosed with stage I-IV CRC were enrolled. MED12 expression was evaluated using immunohistochemistry. The relationships between MED12 loss and clinicopathological characteristics were analyzed. In 100 patients, 79 and 21 patients were classified into MED12 positive and MED12 negative, respectively. MED12 negative was significantly associated with tumor budding, nodal metastasis, and distant metastasis. In conclusion, MED12 loss induces activation of TGF-β pathway resulting EMT. In future, treatment strategy for patients with MED12 loss may improve the prognosis of patients with CRC.

Research Products

• [Journal Article] Feasibility of restorative proctocolectomy in patients with ulcerative colitis-associated lower rectal cancer: A retrospective study. (2018)
  • Author(s): Hotta S, Shimada Y, Nakano M, Yamada S, Abe K, Oyanagi H, Yagi R, Tajima Y, Nakano M, Kameyama H, Nagahashi M, Sakata J, Kobayashi T, Wakai T.
  • Journal Title: Asian Journal of Surgery Volume: 印刷中 Issue: 1 Pages: 267-273
  • DOI: 10.1016/j.asjsur.2018.01.003
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive genomic sequencing detects important genetic differences between right-sided and left-sided colorectal cancer (2017)
  • Author(s): Shimada Y, Kameyama H, Nagahashi M, Ichikawa H, Muneoka Y, Yagi R, Tajima Y, Okamura T, Nakano M, Sakata J, Kobayashi T, Nogami H, Maruyama S, Takii Y, Hayashida T, Takaishi H, Kitagawa Y, Oki E, Konishi T, Ishida F, Kudo SE, Ring JE, Protopopov A, Lyle S, Ling Y, Okuda S, Ishikawa T, Akazawa K, Takabe K, Wakai T.
  • Journal Title: Oncotarget Volume: 24 Issue: 55 Pages: 93567-93579
  • DOI: 10.18632/oncotarget.20510
  • Peer Reviewed / Open Access
• [Journal Article] Utility of comprehensive genomic sequencing for detecting HER2-positive colorectal cancer. (2017)
  • Author(s): Shimada Y, Yagi R, Kameyama H, Nagahashi M, Ichikawa H, Tajima Y, Okamura T, Nakano M, Nakano M, Sato Y, Matsuzawa T, Sakata J, Kobayashi T, Nogami H, Maruyama S, Takii Y, Kawasaki T, Homma KI, Izutsu H, Kodama K, Ring JE, Protopopov A, Lyle S, Okuda S, Akazawa K, Wakai T.
  • Journal Title: Hum Pathol. Volume: 印刷中 Pages: 1-9
  • DOI: 10.1016/j.humpath.2017.02.004
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Association between poorly differentiated clusters and efficacy of 5-fluorouracil-based adjuvant chemotherapy in stage III colorectal cancer. (2017)
  • Author(s): Tajima Y, Shimada Y, Kameyama H, Yagi R, Okamura T, Kobayashi T, Kosugi SI, Wakai T.
  • Journal Title: Jpn J Clin Oncol. Volume: 47 Issue: 4 Pages: 313-320
  • DOI: 10.1093/jjco/hyw209
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinical significance of MED12 expression in colorectal cancer. (2016)
  • Author(s): Shimada Y, Tajima Y, Kameyama H, Yagi R, Okamura T, Hirose Y, Sakata J, Kobayashi T, Matsuda Y, Ajioka Y, Kosugi SI, Wakai T
  • Journal Title: Int J Clin Exp Pathol. Volume: 9 Pages: 6937-44
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 大腸癌における転写メディエーターMED12異常発現の臨床的意義 (2016)
  • Author(s): 島田能史
  • Organizer: 第71回日本消化器外科学会総会
  • Place of Presentation: アスティ徳島（徳島県・徳島市）
  • Year and Date: 2016-07-16
• [Presentation] 大腸癌における転写メディエーターMED12異常発現の臨床的意義． (2016)
  • Author(s): 島田能史，田島陽介，亀山仁史，八木亮磨，岡村拓磨，中野雅人，坂田 純，小林 隆，小杉伸一，若井俊文．
  • Organizer: 第71回日本消化器外科学会総会
  • Place of Presentation: アスティとくしま（徳島県、徳島市）
• [Presentation] MED 12 expression may be a significant prognosis prediction in colorectal cancer. (2016)
  • Author(s): Toge K, Shimada Y, Tajima Y, Kameyama H, Yagi R, Okamura T, Hirose Y, Sakata J, Kobayashi T, Ajioka Y, Wakai T
  • Organizer: 26th World Congress of International Association of Surgeons, Gastroenterologists and Oncologists
  • Place of Presentation: Seoul, Korea
  • Int'l Joint Research