Therapeutic potential of HOPX target genes in CRC

2013 Fiscal Year Final Research Report

• Project/Area Number: 23616005
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: epigenetics
• Research Institution: Kitasato University
• Principal Investigator: OOKI Akira 北里大学, 医学部, 助教 (50348546)
• Project Period (FY): 2011 – 2013
• Keywords: 大腸癌 / HOPX / EphA2 / 未分化 / メチル化

Research Abstract

In colorectal cancer, HOPX hypermethylation is closely associated with poorly differentiated histology. As EphA2 is also known to be characteristics to poorly differentiate histology in CRC, and EphA2 was identified as a potential downstream target of HOPX in our previous studies, we are focusing on EphA2 as a therapeutic target in CRC. EphA2 expression is found in 15 out of poorly differentiated CRC, 12 from moderately differentiated CRC, and only 6 cases of 20 highly differentiated CRC (p=0.0083). We then examined 21 poorly differentiated CRC in detail, and EphA2 expression was recognized in about half cases with HOPX hypermethylation (n=11), while EphA2 expression was defective in 2 cases with HOPX hypomethylation. These finding suggested that HOPX may be causative molecule to overexpress EphA2 in primary CRC. In conclusion, EphA2 might be the optimal therapeutic target in primary CRC.

Research Products

• [Presentation] 消化器癌浸潤転移に関するepigenetic異常同定と癌診断・治療への応用 (2013)
  • Author(s): 山下継史, 加藤弘, 藁谷美奈, 大木暁, 河又寛, 江間玲, 細田桂, 森谷宏光, 桜本信一, 片田夏也, 渡邊昌彦
  • Organizer: 第113回日本外科学会定期学術集会(ポスターセッション(77)「大腸発癌・悪性度-1」)
  • Place of Presentation: 福岡(日本外科学会雑誌, 114(2):626, 2013.)
  • Year and Date: 2013-04-11
• [Presentation] Epigenetic conversion on p53 pathway in human cancer:The clinical potential of p53 mutation status as a predictive biomarker for drug sensitivity by epigenetic treatment (2013)
  • Author(s): Keishi Yamashita, Mina Waraya, Hiroshi Katoh, Akira Ooki, Hiroshi Kawamata, Kazunori Nakamura,Hiroshi Nishimiya, Akira Ema, David Sidransky,Masahiko Watanabe
  • Organizer: AACR 2013: American Association for Cancer Research Annual Meeting 2013
  • Place of Presentation: Washington, D C/ USA
  • Year and Date: 2013-04-10
• [Presentation] 食道扁平上皮癌のEpigenome解析 (2012)
  • Author(s): 山下継史, 藁谷美奈, 加藤弘, 大木暁, 河又寛, 根本昌之, 柴田智隆, 三重野浩朗, 片田夏也, 渡邊昌彦
  • Organizer: 第66回日本食道学会学術集会(シンポジウム3食道癌からサイエンスを考える)
  • Place of Presentation: 軽井沢(日本食道学会学術集会プログラム・抄録集, 66回:136)
  • Year and Date: 2012-06-22
• [Presentation] 大腸がんにおける癌抑制遺伝子HOPXとAP-1(c-Fos/c-Jun)経路のクロスリンクと細胞死 (2012)
  • Author(s): 山下継史, 藁谷美奈, 加藤弘, 大木暁, 渡邊昌彦
  • Organizer: 第112回日本外科学会定期学術集会(サージカルフォーラム(88)「大腸基礎-1(発癌)」
  • Place of Presentation: 千葉(日本外科学会雑誌, 113(2):403)
  • Year and Date: 2012-04-14
• [Presentation] Therapeutic potential of PRL-3 targeting and clinical significance of PRL-3 genomic amplification in gastric cancer (2011)
  • Author(s): Akira Ooki, Keishi Yamashita, Masahiko Watanabe
  • Organizer: ISW2011:International Surgical Week(Poster Exhibition Stomach/Duodenum)
  • Place of Presentation: 横浜市
  • Year and Date: 20110828-0901