Comprehensive analyses of biomarkers predicting therapeutic effect of an anti-angiogenetic agent against advanced colorectal cancer

• Project/Area Number: 15K08963
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: University of Tsukuba
• Principal Investigator: Kojima Hiroshi 筑波大学, 医学医療系, 教授 (10225435)
• Co-Investigator(Kenkyū-buntansha): 大越 靖 筑波大学, 医学医療系, 准教授 (10400673)
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 大腸癌 / bevacizumab / サイトカイン / 血管新生因子 / miRNA / 治療効果予測 / バイオマーカー / Bevacixumab / microRNA / 大腸がん / Bevacitumab / Bevacizumab

Outline of Final Research Achievements

This study was designed to identify biomarkers (BMs) predicting therapeutic effect of an anti-VEGF antibody, bevacizumab against advanced colorectal cancer. Pre- and post-treatment (Tx) serum concentrations of VEGF, pre-Tx cytokine/chemokine profile, and miRNA released after stimulation of human umbilical vein endothelial cells (HUVEC) with VEGF were assayed to select candidate BMs.
Serum concentration of post-Tx Bmab-unconjugated VEGF was significantly higher in non-responders. Comprehensive analysis of pre-Tx cytokines/chemokines revealed that serum concentrations of IL-10 and VEGF were elevated in non-responsive patients. Moreover, patients with higher concentrations of these cytokines showed significantly worse prognosis. These data collectively suggest that IL-10 and VEGF can be predictive BMs. We are currently under investigation by using blood samples obtained from patients to clarify the usefulness of the selected miRNAs through in vitro stimulation of HUVEC with VEGF.

Research Products

• [Journal Article] Endogenous reference RNAs for microRNA quantitation in formalin-fixed, paraffin-embedded lymph node tissue (2018)
  • Author(s): Inada K, Okoshi Y, Cho-Isoda Y, Ishiguro S, Suzuki H, Oki A, Tamaki Y, Shimazui T, Saito H, Hori M, Iijima T, Kojima H
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 5918-5927
  • DOI: 10.1038/s41598-018-24338-7
  • NAID: 120007134247
  • Peer Reviewed / Open Access