ArticleClinical and translational medicine2024
Integrating single-cell and spatial transcriptomes reveals COL4A1/2 facilitates the spatial organisation of stromal cells differentiation in breast phyllodes tumours.
Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Combining Spatial Multi-Omics Data to Decipher Spatial Domains and Elucidate Cell Heterogeneity Based on Self-Supervised Graph Learning.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From Proteomics to Pathology: S100A8's Impact on Breast Phyllodes Tumors Grading.Annals of surgical oncology · 2026Article
- Integrated multi-regional multiomic profiling of breast phyllodes tumours reveals peritumoural immune activation and stromal remodelling.Clinical and translational medicine · 2026Article
- Single-cell profiling of bone metastasis ecosystems reveals pivotal role of INSRTranslational oncology · 2026Article
- Comparative omics reveals conserved extracellular matrix signatures during mammary tumor progression.Frontiers in oncology · 2026Article
- Integrative multi-omics reveals common and distinct pathogenic mechanisms and preoperative diagnostic signatures in breast fibroepithelial lesions.Breast cancer research : BCR · 2025Article
- VASN drives gastric tumorigenesis via activation of the COL4A1/PI3K/AKT axis during Helicobacter pylori infection.British journal of cancer · 2025Article
- Spatial Transcriptomics Decodes Breast Cancer Microenvironment Heterogeneity: From Multidimensional Dynamic Profiling to Precision Therapy Blueprint Construction.Biomolecules · 2025Review
- Comparative transcriptomics of salivary basal cell adenoma and adenocarcinoma sustain linear neoplastic evolution and intertumor heterogeneity: classification and biological implications.The Journal of pathology · 2025Article
- Luminal Stem-like Cells in High-Risk/Locally Advanced Prostate Cancer Promote Resistance to Hormonal Therapy.Theranostics · 2025Article
- Advancements in the Application of scRNA-Seq in Breast Research: A Review.International journal of molecular sciences · 2024Review
- Integrating single-cell and spatial transcriptomes reveals COL4A1/2 facilitates the spatial organisation of stromal cells differentiation in breast phyllodes tumours.Clinical and translational medicine · 2024Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBreast phyllodes tumours (PTs) are a unique type of fibroepithelial neoplasms with metastatic potential and recurrence tendency. However, the precise nature of heterogeneity in breast PTs remains poorly understood. This study aimed to elucidate the cell subpopulations composition and spatial structure and investigate diagnostic markers in the pathogenesis of PTs.
methodsWe applied single-cell RNA sequencing and spatial transcriptomes on tumours and adjacent normal tissues for integration analysis. Immunofluorescence experiments were conducted to verify the tissue distribution of cells. Tumour cells from patients with PTs were cultured to validate the function of genes. To validate the heterogeneity, the epithelial and stromal components of tumour tissues were separated using laser capture microdissection, and microproteomics data were obtained using data-independent acquisition mass spectrometry. The diagnostic value of genes was assessed using immunohistochemistry staining.
resultsTumour stromal cells harboured seven subpopulations. Among them, a population of widely distributed cancer-associated fibroblast-like stroma cells exhibited strong communications with epithelial progenitors which underwent a mesenchymal transition. We identified two stromal subpopulations sharing epithelial progenitors and mesenchymal markers. They were inferred to further differentiate into transcriptionally active stromal subpopulations continuously expressing COL4A1/2. The binding of COL4A1/2 with ITGA1/B1 facilitated a growth pattern from the stroma towards the surrounding glands. Furthermore, we found consistent transcriptional changes between intratumoural heterogeneity and inter-patient heterogeneity by performing microproteomics studies on 30 samples from 11 PTs. The immunohistochemical assessment of 97 independent cohorts identified that COL4A1/2 and CSRP1 could aid in accurate diagnosis and grading.
conclusionsOur study demonstrates that COL4A1/2 shapes the spatial structure of stromal cell differentiation and has important clinical implications for accurate diagnosis of breast PTs.
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