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2023 Fiscal Year Final Research Report

of intratumoural heterogeneity in breast cancer and novel therapeutic strategies using single cell analysis.

Research Project

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Project/Area Number 21K15563
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionNational Cancer Center Japan

Principal Investigator

Shiino Sho  国立研究開発法人国立がん研究センター, 中央病院, 医員 (60784527)

Project Period (FY) 2021-04-01 – 2024-03-31
Keywords乳癌 / シングルセル解析 / 腫瘍内不均一性
Outline of Final Research Achievements

Single-cell gene expression data analyzed within our institution and the respective datasets in public databases were integrated to investigate gene expression for tumor heterogeneity, which contributes to treatment resistance in breast cancer. Cluster analysis identified a heterogeneous distribution of breast cancer-related genes, with different gene expression levels in the ERBB2-high and ERBB2-low expression groups. Moreover, some microRNAs were predicted as upstream regulators of ERBB2 expression. Gene expression levels of CSC (Cancer stem cell) markers, EMT (Epithelial-to-mesenchymal transition) markers and metastasis-related markers differed between each case group. These results suggest that heterogeneity in gene expression may occur not only in the presence or absence of ERBB2 expression and ER status, but also between each patient.

Free Research Field

乳腺外科

Academic Significance and Societal Importance of the Research Achievements

乳癌に対する治療の抵抗性一因として腫瘍内不均一性の形成は重要視されているが、まだその解明と克服には至っていない状況である。HER2陽性乳癌およびLuminal乳癌を対象としたシングル細胞遺伝子発現解析を主体とした本研究において、腫瘍内における遺伝子発現レベルが各細胞間で異なること、さらには症例間でも遺伝子発現の不均一性が認められる可能性が見出された。乳癌の治療にあたる上で、将来的に腫瘍本来の不均一な性質に基づいた治療を展開していく必要性があるのみならず、各患者の遺伝子発現の特徴にも応じたテーラーメイド的な治療が将来的に治療抵抗性の克服を考慮する上で必要になる可能性が示唆された。

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Published: 2025-01-30  

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