Establishment of a Breast Cancer Prognostic Model Based on HOX Gene Expression and Wnt Pathway Activity

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23897
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Keio University
• Principal Investigator: Yokoe Takamichi 慶應義塾大学, 医学部(信濃町), 助教 (90649956)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: HOX遺伝子 / Luminal乳癌 / クラスタリング / 予後予測 / 共変動解析

Outline of Final Research Achievements

The HOX gene group is a master regulator of development during the embryonic period. It has recently been reported that HOX gene is involved in the development and progression of malignant tumors. The overall function of HOX genes has not yet been elucidated. The purpose of this study was to clarify the relationship between the expression pattern of HOX genes in luminal breast cancer and Wnt pathway, and also between HOX gene expression pattern and clinical prognosis. Analysis of public data revealed that the HOX-C10 gene plays a central role in dividing the prognosis of Luminal breast cancer. It was also shown that the prognosis of luminal breast cancer can be accurately predicted using a prognosis prediction algorithm based on the HOX signature (sensitivity 61%, specificity 64%).

Free Research Field

乳癌

Academic Significance and Societal Importance of the Research Achievements

過去のHOX遺伝子と乳癌に関する報告は、個々のHOX遺伝子に注目した検討に留まっている。本研究ではHOX遺伝子全体に着目し、乳癌の臨床病理学的データと統合して網羅的な解析を行った点で、学術的貢献度が高いと言える。ホルモン陽性乳癌の予後予測は補助化学療法の施行の判断に直結するため、OncotypeDX等の様々な多遺伝子アッセイが商用化されているが、いずれも乳癌の全遺伝子発現をクラスター分類して予後と相関させている。本研究では、一貫した機能を持つと考えられる単一のHOX遺伝子ファミリーの機能解析を通じて予後予測を行っており、他の多遺伝子アッセイとは異なる新しい方法で臨床に貢献する研究となった。