Significance of genetic alterations and glycosylation in PD-L1 and their biomarker development

• Project/Area Number: 17K09638
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Hokkaido University
• Principal Investigator: Akita Hirotoshi 北海道大学, 大学病院, 教授 (70222528)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 非小細胞肺癌 / PD-L1タンパク質発現 / PD-L1遺伝子変異 / PD-L1遺伝子変異解析 / 内科 / ゲノム / 糖鎖

Outline of Final Research Achievements

We explored new biomarkers in non-small cell lung cancers (NSCLCs).
We studied PD-L1 expression by IHC in 154 surgically resected NSCLC specimens, and found H score > or = 10% in 46.8 % of specimens, which were associated with squamous cell carcinoma compared with adenocarcinoma, and with smoking.
We studied SNP in PD-L1 3’UTR miRNA seeding region by NGS in 126 surgically resected NSCLC specimens, and found higher PD-L1 expression in the cancer/normal-matched group (52/114) than the cancer/normal-mismatched group (10/12) (P = 0.01).

Academic Significance and Societal Importance of the Research Achievements

抗PD-1/PD-L1抗体薬の治療効果予測因子は、肺癌においてはPD-L1免疫染色であるが、同一腫瘍内の不均一性や臨床経過による変化があり、より“固定的で安定な”治療効果予測因子の開発が求められる。本研究では、PD-L1遺伝子の遺伝子変異（SNP）に着目し、新たなバイオマーカー（抗PD-1/PD-L1抗体薬の治療効果予測因子）を探索した意義は極めて大きく、今後、肺癌のみならず、肺癌以外の癌腫においても参考になるものと考えられる。

Research Products

• [Presentation] Clinicopathological features of programmed cell death ligand 1 (PD-L1) expression in resected non-small cell lung cancers (2019)
  • Author(s): Ohhara Y, Akita H, et al.
  • Organizer: American Association for Cancer Research (AACR) Annual Meeting
  • Int'l Joint Research