Development of a sensitive epigenomic biomarker for urothelial cancer

• Project/Area Number: 15K15584
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Sapporo Medical University
• Principal Investigator: Suzuki Hiromu 札幌医科大学, 医学部, 教授 (20381254)
• Co-Investigator(Renkei-kenkyūsha): MASUMORI Naoya 札幌医科大学, 医学部, 教授 (20295356)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 膀胱がん / DNAメチル化 / miRNA / 診断マーカー / 再発予測 / 尿路上皮がん / バイオマーカー / 再発診断

Outline of Final Research Achievements

It is now apparent that BCa is a genetic and epigenetic disease, and that aberrant methylation of a number of tumor-related genes is involved in BCa. Moreover, several studies have shown that urinary DNA methylation may be a useful marker for BCa diagnosis. MicroRNAs (miRNAs), which are small noncoding RNAs that post-transcriptionally regulate gene expression, have also been strongly implicated in BCa. We identified a set of miRNA genes whose promoter CpG islands are prevalently hypermethylated in BCa cells. We prospectively collected self-voided urine samples from non-muscle invasive BCa (NMIBC) who had undergone transurethral resection of BCa. We found that the number of methylated genes (M-score) and quantitative levels of methylation in the urine specimens are strongly associated with current and late intravesical recurrence of BCa. Our data suggest that urinary methylation of miRNA genes may be a useful marker for detecting and predicting BCa recurrence.

Research Products

• [Journal Article] TET1 Depletion Induces Aberrant CpG Methylation in Colorectal Cancer Cells. (2016)
  • Author(s): Kai M, Niinuma T, Kitajima H, Yamamoto E, Harada T, Aoki H, Maruyama R, Toyota M, Sasaki Y, Sugai T, Tokino T, Nakase H, Suzuki H.
  • Journal Title: PLoS One Volume: 11 Issue: 12 Pages: e0168281-e0168281
  • DOI: 10.1371/journal.pone.0168281
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A genomic screen for long noncoding RNA genes epigenetically silenced by aberrant DNA methylation in colorectal cancer. (2016)
  • Author(s): Kumegawa K, Maruyama R, Yamamoto E, Ashida M, Kitajima H, Tsuyada A, Niinuma T, Kai M, Yamano HO, Sugai T, Tokino T, Shinomura Y, Imai K, Suzuki H.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 26699-26699
  • DOI: 10.1038/srep26699
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic silencing of NTSR1 is associated with lateral and noninvasive growth of colorectal tumors (2015)
  • Author(s): Kamimae S, Yamamoto E, Kai M, Niinuma T, Yamano HO, Nojima M, Yoshikawa K, Kimura T, Takagi R, Harada E, Harada T, Maruyama R, Sasaki Y, Tokino T, Shinomura Y, Sugai T, Imai K, Suzuki H
  • Journal Title: Oncotarget Volume: 6 Issue: 30 Pages: 29975-90
  • DOI: 10.18632/oncotarget.5034
  • NAID: 130005161526
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A Screen for Epigenetically Silenced microRNA Genes in Gastrointestinal Stromal Tumors. (2015)
  • Author(s): Isosaka M, Niinuma T, Nojima M, Kai M, Yamamoto E, Maruyama R, Nobuoka T, Nishida T, Kanda T, Taguchi T, Hasegawa T, Tokino T, Hirata K, Suzuki H, Shinomura Y
  • Journal Title: PLoS One Volume: 10 Issue: 7 Pages: e0133754-e0133754
  • DOI: 10.1371/journal.pone.0133754
  • Peer Reviewed / Open Access
• [Presentation] 膀胱癌におけるシスプラチン耐性に関与するマイクロRNAの同定 (2016)
  • Author(s): 進藤哲哉、西山直隆、丸山玲緒、新沼猛、北嶋洋志、甲斐正広、時野隆至、鈴木拓、舛森直哉
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-06
• [Presentation] Identification of microRNAs dysregulated in gemcitabine and cisplatin resistant bladder cancer cells. (2016)
  • Author(s): Tetsuya Shindo, Reo Maruyama, Naotaka Nishiyama, Hiroshi Kitamura, Hiromu Suzuki, Naoya Masumori
  • Organizer: Tenth AACR-JCA Joint Conference
  • Place of Presentation: Maui, Hawaii, USA
  • Year and Date: 2016-02-16
  • Int'l Joint Research
• [Presentation] 尿中DNAメチル化解析による膀胱がん再発診断法の開発 (2016)
  • Author(s): 進藤哲哉、清水崇、西山直隆、新沼猛、北嶋洋志、甲斐正広、伊東直樹、舛森直哉、鈴木拓
  • Organizer: 第36回日本分子腫瘍マーカー研究会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）