Development of a risk stratification method for lung cancer based on immune profiles
| Project/Area Number |
20H03695
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | National Cancer Center Japan |
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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)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
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| Keywords | 肺がん / 生殖細胞系列変異 / HLA多様性 / 肺腺がん / HLAアリル / 次世代シークエンス / 体細胞変異 / 治療効果 / 化学療法応答性 / 免疫チェックポイント阻害剤 / 発がん / 化学療法 / HLA |
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| Outline of Research at the Start |
本研究では、肺がんで主要に認められるドライバー変異や組織型別での発がんリスクとの関連を明らかにする。さらに発がんリスクに関わるHLAアリルやバリアントが術後再発予後やプラチナダブレット療法の応答性に関連するかを明らかにする。肺がん特異的なHLAリスク/プロテクティブアリルが認められた症例由来のがん組織を用いた全エクソン・RNAシークエンスデータを用いて、ネオアンチゲンの推定とHLAアリルとの結合能の推定を行う。初年度は既に取得されているゲノムデータを統合するとともに、ネオアンチゲン解析に必要ながんゲノムデータの取得を行う。2年次以降は、得られたゲノムデータを用いた関連解析を実施する。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Vaginal Transmission of Cancer from Mothers with Cervical Cancer to Infants2021
Author(s)
Arakawa A, Ichikawa H, Kubo T, Motoi N, Kumamoto T, Nakajima M, Yonemori K, Noguchi E, Sunami K, Shiraishi K, Kakishima H, Yoshida H, Hishiki T, Kawakubo N, Kuroda T, Kiyokawa T, Yamada K, Yanaihara N, et al, and Kohno T, Ogawa C.
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Journal Title
New England Journal of Medicine
Volume: 384
Issue: 1
Pages: 42-50
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases2020
Author(s)
Ishigaki K, Akiyama M, Kanai M, Takahashi A, Kawakami E, Sugishita H, Sakaue S, Matoba N, Low SK, Okada Y, Yamaji T, et al
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Journal Title
Nature Genetics
Volume: 52
Issue: 7
Pages: 669-679
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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