Analysis of microRNA in the cancer cell and stromal tissue to explore predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer.

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16558
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Yamaguchi University
• Principal Investigator: TAKENOUCHI Hiroko 山口大学, 医学部, 特別医学研究員 (20749808)
• Research Collaborator: HAZAMA Shoichi ; SUZUKI Nobuaki
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: マイクロRNA / 癌微小環境 / がん免疫療法 / バイオマーカー

Outline of Final Research Achievements

Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of this study was to explore microRNAs as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. We conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Subsequently, we carried out RT-PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR-125b-1 in cancer cells , and miR-378a in both cancer cells and stromal cells. In conclusion, miR-125b-1 and miR-378a expression might be considered as novel biomarkers to predict the efficacy of vaccine treatment against colorectal cancer.

Free Research Field

腫瘍・免疫学

Academic Significance and Societal Importance of the Research Achievements

がん免疫療法は近年注目され、開発が進んでいる領域であるが、免疫療法は患者によって効果に個人差があり、治療前にその効果を適切に予測できる方法の開発が重要である。
本研究では、Laser capture microdissection法により、がん組織をがん細胞と間質細胞に切り分け、各々のマイクロRNA発現量と免疫療法の治療効果との関連を解析したことで、がん細胞および間質部のmiR-125b-1ならびにmiR-378aが、免疫療法の効果と関連する有用なバイオマーカーとなり得る可能性を見出した。