Investigation of the functions and the roles of LY6D as a novel cancer stem-cell marker of non-small cell lung cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16515
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Kumamoto University
• Principal Investigator: Semba Takashi 熊本大学, 国際先端医学研究機構, 客員講師 (30897682)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 肺癌 / 癌幹細胞 / LY6D / 遺伝子改変マウス

Outline of Final Research Achievements

The expression of LY6D in resected non-small cell lung cancer (NSCLC) tissues from patients was evaluated by immunohistochemistry with clinical outcome information. We found that LY6D-high patients showed shorter relapse-free survival than LY6D-low patients. Transcriptomic and tumor microenvironment analysis using publicly available RNA-seq database revealed upregulated neutrophil-associated signals and increased neutrophil infiltration into tumor in LY6D-high patients with NSCLC. Furthermore, we developed a novel Ly6d conditional knockout mouse that enable to investigate the functions and roles of Ly6d in vivo.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

LY6Dの発現と術後再発予後との相関を見出した。また、そのメカニズムとして、癌幹細胞の制御以外に、腫瘍の転移や再発に重要な役割を担っていることが近年明らかとなっている腫瘍関連好中球Tumor-associated neutrophil（TAN）の浸潤や活性化にLY6Dが関わっている可能性が示唆された。さらに、LY6Dのコンディショナルノックアウトマウスの作製はこれまでに報告がなく、この遺伝子改変マウスの開発により生体でのLY6Dの詳細な機能評価が可能となった。