Endoscopic and molecular analysis in colorectal serrated lesions

• Project/Area Number: 17K15959
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: Hideki Wakasugi 札幌医科大学, 医学部, 研究員 (90784314)
• Research Collaborator: SUZUKI Hiromu ; YAMAMOTO Eiichiro ; Aoki Hironori ; YAMANO Hiro-o ; SUGAI Tamotsu
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 大腸がん / 前癌病変 / DNAメチル化 / 鋸歯状病変 / メチル化 / 大腸腫瘍 / 拡大内視鏡 / エピジェネティクス

Outline of Final Research Achievements

We aimed to identify epigenetic alterations that are associated with the development of TSA. The Infinium HumanMethylation450 (HM450) BeadChip array analysis identified that SMOC1 gene was frequently methylated in TSAs. RT-PCR revealed that SMOC1 is abundantly expressed in normal colon and SSA/Ps, but is significantly downregulated in TSAs. Immunohistochemical analysis showed that SMOC1 was expressed in the epithelium of normal colonic tissues and SSA/Ps, but that expression is significantly reduced in TSAs.Methylation of SMOC1 is associated with TSA development but is rarely observed in SSA/Ps. Immunohistochemical analysis of SMOC1 may be a useful marker to discriminate between SSA/Ps and TSAs. Our data suggests SMOC1 methylation may play a role in the neoplastic pathways arising in TSAs.

Academic Significance and Societal Importance of the Research Achievements

SMOC1のメチル化、発現が鑑別困難な鋸歯状病変の診断バイオマーカーとして役立ち、SMOC1のメチル化が大腸がん発症リスクの高い前駆病変の予測マーカーになり得ることが示唆される。発がんリスクの高い前癌病変が同定することができれば発がん予防、大腸がん死減少に貢献できるものと考える。

Research Products

• [Journal Article] DOT1L inhibition blocks multiple myeloma cell proliferation by suppressing IRF4-MYC signaling (2018)
  • Author(s): Ishiguro Kazuya、Kitajima Hiroshi、Niinuma Takeshi、Ishida Tadao、Maruyama Reo、Ikeda Hiroshi、Hayashi Toshiaki、Sasaki Hajime、Wakasugi Hideki、Nishiyama Koyo、Shindo Tetsuya、Yamamoto Eiichiro、Kai Masahiro、Sasaki Yasushi、Tokino Takashi、Nakase Hiroshi、Suzuki Hiromu
  • Journal Title: Haematologica Volume: 104 Issue: 1 Pages: 155-165
  • DOI: 10.3324/haematol.2018.191262
  • Peer Reviewed / Open Access
• [Journal Article] Dysregulation of miRNA in chronic hepatitis B is associated with hepatocellular carcinoma risk after nucleos(t)ide analogue treatment (2018)
  • Author(s): Wakasugi H, Takahashi H, Niinuma T, Kitajima H, Oikawa R, Matsumoto N, Takeba Y, Otsubo T, Takagi M, Ariizumi Y, Suzuki M, Okuse C, Iwabuchi S, Nakano M, Akutsu N, Kang JH, Matsui T, Yamada N, Sasaki H, Yamamoto E, Kai M, Sasaki Y, Sasaki, Tanaka, Yotsuyanagi, Tsutsumi, Yamamoto, Tokino T , Nakase H, Suzuki H, Itoh F
  • Journal Title: Cancer Letters Volume: 434 Pages: 91-100
  • DOI: 10.1016/j.canlet.2018.07.019
  • Peer Reviewed