Development of a risk stratification method for lung cancer based on immune profiles

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03695
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: Shiraishi Kouya 国立研究開発法人国立がん研究センター, 研究所, 部門長 (80609719)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肺がん / 生殖細胞系列変異 / HLA多様性

Outline of Final Research Achievements

Our investigation revealed significant associations between LADC risk and 19 genomic loci, characterized by highly noteworthy P-values ranging from 6.9 × 10－11 to 4.8 × 10－134. The presence of 10 loci previously reported in the Asian population, as well as two loci reported in the Caucasian population, was validated in our study. Additionally, seven novel loci (PTPRG, TERC, BTN2A1, HLA-C, HLA-DQB1, BAK1, and ASB15) were identified through our investigation. Notably, the biological effects of other loci identified in the present study were also inferred through differential expression in normal lung or blood cells associated with the presence of LADC-risk-associated SNPs; SECISBP2L, BAK1, and BTN2A1 (which encodes a butyrophilin-like protein involved in the regulation of γδ T-cell development and differentiation). Therefore, it is likely that the identified risk-associated loci exert an impact on LADC development and immune evasion.

Free Research Field

がんゲノム解析

Academic Significance and Societal Importance of the Research Achievements

本研究を通して、肺腺がんの発症リスクには数十の感受性遺伝子座が寄与していることを明らかにし、その中にはMHC領域に多くの独立した因子を同定するに至った。これらの感受性遺伝子座を組み合わせたpolygenic risk scoreを算出することで、高リスク群を同定し、肺がんに対する高リスク群の層別化手法の構築に繋げられた。今後は臨床検体を用いてがん組織中の免疫プロファイルとの統合解析をさらに実施し、発症要因のメカニズムを明らかにする予定である。