Is the activity of morphogenesis-related signaling pathways useful to predict survival in stage II colorectal cancer?

• Project/Area Number: 25861220
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: AKIYOSHI Takashi 公益財団法人がん研究会, その他部局等, その他 (50625598)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 大腸癌 / 形態形成シグナル

Outline of Final Research Achievements

We investigated the nuclear Notch1 and Notch3 protein expression by immunohistochemistry as a surrogate marker of activated Notch signaling in stage II and III colorectal cancer, and showed that nuclear Notch3 expression was strongly associated with distant relapse-free survival in stage II colorectal cancer. Biopsy samples were taken from patients with clinical stage II and III rectal cancer during colonoscopic examinations, and we isolated total RNA from cancer cells using laser capture microdissection. Gene expression microarray analysis was performed, and Wnt activity levels were evaluated by single-sample Gene Set Enrichment Analysis. The high Wnt activity levels tended to be inversely associated with recurrence. These findings suggest that the activity of Notch and Wnt signaling are useful in predicting survival in stage II colorectal cancer.

Research Products

• [Journal Article] Laparoscopic salvage surgery for locally recurrent rectal cancer (2014)
  • Author(s): Nagasaki T, Akiyoshi Tet al.
  • Journal Title: J gastrointest Surg Volume: 18 Issue: 4 Pages: 1319-1326
  • DOI: 10.1007/s00595-014-0925-1
  • Peer Reviewed
• [Journal Article] Laparoscopic local excision and rectoanal anastomosis for rectal gastrointestinal stromal tumor: modified laparoscopic intersphincteric resection technique (2014)
  • Author(s): Akiyoshi T et al.
  • Journal Title: Dis Colon Rectum Volume: 57 Issue: 7 Pages: 900-904
  • DOI: 10.1097/dcr.0000000000000146
  • Peer Reviewed
• [Journal Article] Selective Lateral Pelvic Lymph Node Dissection in Patients with Advanced Low Rectal Cancer Treated with Preoperative Chemoradiotherapy Based on Pretreatment Imaging. (2014)
  • Author(s): Akiyoshi T, Ueno M, Matsueda K, Konishi T, Fujimoto Y, Nagayama S, Fukunaga Y, Unno T, Kano A, Kuroyanagi H, Oya M, Yamaguchi T, Watanabe T, Muto T.
  • Journal Title: Ann Surg Oncol Volume: 21(1) Issue: 1 Pages: 189-96
  • DOI: 10.1245/s10434-013-3216-y
  • Peer Reviewed
• [Journal Article] Prediction of response to preoperative chemoradiotherapy in rectal cancer by using reverse transcriptase polymerase chain reaction analysis of four genes (2014)
  • Author(s): Watanabe T, Kobunai T, Akiyoshi T, Matsuda K, Ishihara S, Nozawa K.
  • Journal Title: Dis Colon Rectum. Volume: 57 Issue: 1 Pages: 23
  • DOI: 10.1097/01.dcr.0000437688.33795.9d
  • Peer Reviewed
• [Journal Article] Nuclear Notch3 expression is associated with tumor recurrence in patients with stage II and III colorectal cancer. (2014)
  • Author(s): Ozawa T, Kazama S, Akiyoshi T, Murono K, Yoneyama S, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, Nozawa H, Kanazawa T, Yamaguchi H, Ishihara S, Sunami E, Kitayama J, Morikawa T, Fukayama M, Watanabe T.
  • Journal Title: Ann Surg Oncol Volume: 21 Issue: 8 Pages: 2650-8
  • DOI: 10.1245/s10434-014-3659-9
  • Peer Reviewed