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Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
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Molecular features of luminal breast cancer defined through spatial and single-cell transcriptomics
Ryohei Yoshitake1, Hitomi Mori1,2, Desiree Ha1
1Department of Cancer Biology and Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, California, USA.
Clinical and Translational Medicine
|January 29, 2024
Summary
Intratumour heterogeneity in oestrogen receptor-positive breast cancer is driven by distinct cell populations. Proliferative cells, not oestrogen-responsive ones, are key to tumour growth and aggressive luminal B subtypes.
Area of Science:
- Oncology
- Genomics
- Cancer Biology
Background:
- Intratumour heterogeneity is a key feature of solid tumours, including breast cancer.
- Spatial transcriptomics and single-cell RNA-sequencing are powerful tools for dissecting tumour microenvironments.
Purpose of the Study:
- To profile spatially resolved cell populations in oestrogen receptor-positive (ER+) breast cancer patient-derived xenografts (PDXs).
- To elucidate the role of these cell populations in oestrogen-dependent tumour growth.
Main Methods:
- Investigated two ER+ breast cancer PDXs with differing oestrogen-mediated growth responses (GS3 and SC31).
- Validated findings using single-cell analysis on an ER-low PDX (GS1), public datasets, and immunohistochemistry (IHC).
- Assessed translational implications through clinical outcome analyses of public cohorts.
Main Results:
- Identified four distinct, functionally diverse spatial compartments within ER+ breast cancers: oestrogen-responsive, proliferative, hypoxia-induced, and inflammation-related.
- The proliferative compartment, not the oestrogen-responsive one, was critical for oestrogen-dependent tumour growth and Luminal B features.
- Gene signatures from proliferative, hypoxia, and inflammation compartments correlated with worse outcomes; oestrogen-responsive signature correlated with better outcomes.
Conclusions:
- The 'proliferative' cell population is a critical determinant of luminal cancer subtypes, particularly Luminal B breast cancer.
- This proliferative cell population contributes to the aggressive behaviour of Luminal B breast cancer.
