Elucidation of the pathogenesis of malignant mesothelioma based on genetic abnormalities and therapeutic targets for genomic medicine

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09292
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Aichi Medical University
• Principal Investigator: Sivasundaram Karnan 愛知医科大学, 医学部, 講師 (30557096)
• Co-Investigator(Kenkyū-buntansha): 村上 秀樹 愛知医科大学, 愛知医科大学, 客員研究員 (90303619)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: MPM / NF2 / p16 / CD24

Outline of Final Research Achievements

Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleura that is currently incurable due to the lack of an effective early diagnostic method and specific medication. The CDKN2A (p16) and NF2 genes are both frequently mutated in MPM. To understand how these mutations contribute to MPM tumor growth, we generated NF2/p16 double-knockout (DKO) cell clones using human MeT-5A and HOMC-B1 mesothelial cell lines. Quantitative PCR analys showed upregulation of CD24 in DKO clones. CD24 was highly expressed in human mesothelioma tissues and associated with the loss of NF2 and p16. Public data analysis revealed a significantly shorter survival time in MPM patients with high CD24 gene expression levels. These results strongly indicate the potential use of CD24 as a prognostic marker as well as a novel diagnostic and therapeutic target for MPM.

Free Research Field

がん研究

Academic Significance and Societal Importance of the Research Achievements

本研究では、NF2欠損に加えてMPM患者で高頻度に見られるp16INK4欠損やBAP1欠損を二重または三重欠損させた細胞を樹立して、その表現型を動物モデルや分子生物学的手法で解明することにより、新たな早期診断マーカーや分子標的治療薬の候補分子の同定が期待できる。本研究から解き明かされる悪性中皮腫の発がん分子病態は極めて高い新規性とゲノム医療への応用が期待できる。また、本研究における解析システムは、他の癌種の分子病態と発がん機構の解析に応用できる可能性を秘めており、その波及的効果は高い。