Identification of cellular networks that sustain chemoresistance of ovarian clear cell cancers through single nucleus analysis of frozen surgical specimens

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22826
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: National Cancer Center Japan
• Principal Investigator: Mori Yutaro 国立研究開発法人国立がん研究センター, 研究所, 特任研究員 (80883313)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 卵巣明細胞腺癌 / シングルセル解析 / 空間的トランスクリプトーム / 治療抵抗性

Outline of Final Research Achievements

Recent studies suggest that intra-tumor heterogeneity of cancer is profoundly associated with chemoresistance: cancer cells can be stratified into a several distinct populations, some of which co-operate with surrounding non-cancer cells to form cellular networks that sustain chemoresistance.
In this study, we performed single-nucleus RNA-seq analyses and spatial transcriptome of frozen surgical specimens of ovarian clear cell adenocarcinoma and we did integrate analysis of both. Integrated analysis revealed that chemoresistant cancer population was mainly localized in the mixed area of cancer cells and cancer associated fibroblasts.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では難治性の卵巣明細胞腺癌組織のシングル核解析と空間的トランスクリプトーム解析を通じて、治療抵抗性癌細胞と癌関連線維芽細胞の共生・相互作用が治療抵抗性を担っている事を見出した。この共生・相互作用を阻害する事で卵巣明細胞腺癌の治療抵抗性を解除できる可能性があり、今後の新規治療法の開発につながると考える。