Elucidation of Genetic Abnormalities Involved in the Early Development of Small Cell Lung Cancer: An Exploration Focused on Combined Small Cell Lung Cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15403
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Chiba University
• Principal Investigator: Ota Masayuki 千葉大学, 大学院医学研究院, 助教 (40866612)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 肺がん / 混合型小細胞肺癌 / 小細胞肺癌 / 分子サブタイプ

Outline of Final Research Achievements

I analyzed molecular subtypes, neuroendocrine differentiation, and genetic abnormalities in human tumor tissues, focusing on combined small cell lung cancer (SCLC). The proportion of subtypes in pure SCLC showed a similar trend to previous studies using human samples. However, contrary to previous studies suggesting a high frequency of the POU2F3 subtype in the SCLC component of combined SCLC, my findings indicated that this subtype is less prevalent. Considering the genetic abnormalities inferred from the analysis of p53 and RB in each component, I suggest that the development of combined SCLC does not necessarily follow a unidirectional progression from non-small cell lung cancer to SCLC components.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

小細胞肺癌の一部に神経内分泌マーカーの発現が乏しい一群が存在し、これらがPOU2F3サブタイプと相関することが確認された。しかしながら、POU2F3サブタイプが混合型小細胞肺癌で頻度が高いかどうかは議論の余地がある。さらなる解明のために症例の集積を要するとともに、腫瘍型の基盤となる病理組織学的な評価の重要性が改めて浮き彫りになった。
遺伝子異常や小細胞肺癌成分の成り立ちの観点で、混合型小細胞肺癌の一部は通常の小細胞肺癌に対する治療とは異なる反応を示す可能性があると考えられ、新たな治療戦略を構築できる可能性を得られた。