2022 Fiscal Year Final Research Report

Single-cell analysis of neuroendocrine prostate cancer to elucidate pathophysiology and establish novel treatment strategy

Research Project

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Project/Area Number	21K19579
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research Institution	Keio University
Principal Investigator	Kosaka Takeo 慶應義塾大学, 医学部(信濃町), 講師 (30445407)
Co-Investigator(Kenkyū-buntansha)	植田幸嗣公益財団法人がん研究会, がんプレシジョン医療研究センターがんオーダーメイド医療開発プロジェクト, プロジェクトリーダー (10509110) 西原広史慶應義塾大学, 医学部(信濃町), 教授 (50322805) 北野滋久公益財団法人がん研究会, 有明病院がん免疫治療開発部, 部長 (60402682)
Project Period (FY)	2021-07-09 – 2023-03-31
Keywords	神経内分泌がん / リキッドバイオプシー / シングルセル解析 / 次世代シーケンサー / 前立腺癌
Outline of Final Research Achievements	The emergence of treatment-emergent Neuroendocrine Prostate Cancer (tNEPC) has become a clinical problem. Whole-transcriptome analysis using the latest spatial gene expression analysis system in NEPC specimens shows residual expression of the androgen receptor, heterogeneous differences in the expression of downstream AR target factors including PSA, and AR-negative. In addition, NEPC marker-negative portions were also heterogeneously present. By single-cell analysis of circulating tumor cells (CTCs), we found heterogeneity of RNA expression in CTCs among patients and identified several candidate biomarkers characteristic of neuroendocrine transformation.
Free Research Field	シングルセル解析
Academic Significance and Societal Importance of the Research Achievements	組織切片における空間的遺伝子発現解析による活性化遺伝子の3次元地図情報と、NEPC患者の血液循環腫瘍細胞(CTC)のシングルセル解析を統合解析することで、NEPCに存在するITHの理解と、ITHの制御を可能とする標的分子を同定した。今後の新規治療戦略確立のための基盤となる研究成果である