Comprehensive analysis of the homeobox family genes in breast cancer demonstrates their similar roles in cancer and development

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17591
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Keio University
• Principal Investigator: ODANI Erina 慶應義塾大学, 医学部(信濃町), 助教 (70868398)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: HOX遺伝子群 / 乳癌

Outline of Final Research Achievements

To get to the essence of the HOX genes, which are highly homologous and linked, these comprehensive analyses were considered necessary. We used 512 TCGA breast cancer array data to calculate the covariations between the genes in breast cancer. We found out that HOX genes covariate the most with other HOX genes, especially within the chromosomally proximal groups. However, in the normal breast tissue, the expression of HOX genes was random, and much fewer correlations were observed among HOX genes. Furthermore, when we compared Luminal A and B classified by PAM50, co-variation was more strongly observed in Luminal B, which is considered to be more malignant. HOX genes strongly interact with each other in breast cancer, similar to that during development, contrary to the findings observed for normal breast tissue.

Free Research Field

乳腺外科

Academic Significance and Societal Importance of the Research Achievements

HOX遺伝子群の発現は腫瘍内で強く連動し合い、サブタイプ毎に連動パターンが異なること、またLuminal B症例ではHOX遺伝子群の発現パターンにより予後が規定されることが判明した。すなわち、HOX遺伝子群の網羅的解析により、乳癌の予後を規定することができ、発生時にHOX遺伝子の上流シグナルとして働くWnt経路の活性化を反映していると考えられた。これらの結果から胎生期にHOX遺伝子の強い共変動がみられることと同様の現象が、予後不良な乳癌にも認められ、胎生期と癌におけるHOX遺伝子群の挙動に関して興味深い類似性が示唆され、腫瘍生物学的に重要な意義を持つと考えられた。