Analysis of microbiome and epigenetics for the development of novel biomarker in Gastrointestinal cancers

2020 Fiscal Year Final Research Report

• Project/Area Number: 17KK0195
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Kumamoto University
• Principal Investigator: BABA Yoshifumi 熊本大学, 病院, 特任准教授 (20599708)
• Project Period (FY): 2018 – 2020
• Keywords: 腸内細菌 / 食道癌 / エピジェネティクス / LINE-1 / Fusobacterium nucleatum

Outline of Final Research Achievements

We previously demonstrated the relationship of human microbiome Fusobacterium nucleatum with unfavorable clinical outcomes and inferior chemotherapeutic responses in esophageal cancer. Global DNA methylation is associated with the occurrence and development of various cancers. In our previous study, LINE-1 hypomethylation (i.e., global DNA hypomethylation) was associated with a poor prognosis in esophageal cancer. As the gut microbiota may play crucial roles in the DNA methylation of host cells, we hypothesized that F. nucleatum might influence LINE-1 methylation levels in esophageal cancer.F. nucleatum DNA was related to the LINE-1 hypomethylation of tumor lesions in esophageal cancer (P < 0.0001). We found that the impact of F. nucleatum on clinical outcomes was not modified by LINE-1 hypomethylation (for interaction P = 0.014).

Free Research Field

外科腫瘍学、腫瘍免疫学、腸内細菌、エピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

腸内細菌叢はプロバイオティクス（Probiotics；人体に有益な腸内細菌叢ならびにこれらを含む食品・製品）やプレバイオティクス（Prebiotics；腸内細菌叢のバランスを改善する作用がある物質）により後天的に変化させることができる。今後の研究において、食道扁平上皮癌におけるFusobacteriumとエピジェネティクスの関係がより詳細に解明されれば、がん治療の新たな創薬に繋がる可能性があると考えている。