ArticleJournal of translational medicine2025
Integration of single-cell and spatial transcriptomics reveals fibroblast subtypes in hepatocellular carcinoma: spatial distribution, differentiation trajectories, and therapeutic potential.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Cancer-associated fibroblasts in therapeutic resistance of hepatocellular carcinoma: evidence, mechanisms, and translational implications.Medical oncology (Northwood, London, England) · 2026Review
- Unveiling the role of spatial transcriptomics in the analysis of the tumor immune microenvironment (Review).International journal of molecular medicine · 2026Review
- Deep Learning-Assisted Prioritization of Candidate Drug Targets in Tumors Using Spatial Multi-Omics.Biology · 2026Review
- Single-cell spatial landscape of aggrephagy activity stratifies hepatocellular carcinoma neutrophils and delivers a 5-gene diagnostic panel for patient stratification.Translational oncology · 2026Article
- Single-cell profiling reveals a novel CAF subpopulation linking stromal heterogeneity to immune suppression in breast cancer subtypes.Journal of translational medicine · 2026Article
- HMGA2 identified via m6A-senescence multi-omics in laryngeal squamous cell carcinoma.Scientific reports · 2026Article
- Methyltransferase-Like 14 Promotes the Angiogenesis of Hepatocellular Carcinoma via Targeting Vascular Endothelial Growth Factor A.Cancer reports (Hoboken, N.J.) · 2026Article
- Understanding how hypoxia contributes to liver cancer stem cells maintenance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- ASCL2-mediated macrophage-myofibroblast transition generates immunosuppressive CAF_7 in NSCLC bone metastases.Journal of experimental & clinical cancer research : CR · 2026Article
- Targeting Tumor-Associated Macrophages and Cancer-Associated Fibroblasts to Overcome Therapeutic Resistance in Hepatocellular Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Cancer-Associated Fibroblasts Functions as Multifunctional Architects of the Tumor Stroma and Represent Emerging Therapeutic Vulnerabilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- POSTNOncology reports · 2026Article
- Integrative bibliometrics and spatial transcriptomics identify CAF-associated genes and immune niches in hepatocellular carcinoma.Discover oncology · 2026Article
- Pleiotropic mechanisms of cancer-associated fibroblast-mediated resistance in hepatocellular carcinoma: emerging therapeutic vulnerabilities and targeting strategies.Cancer gene therapy · 2026Review
- Exploring single-cell and multi-omics technologies and their role in unraveling tumor heterogeneity of hepatocellular carcinoma.Journal of liver cancer · 2026Review
- Cancer-associated fibroblasts as a critical driver in tumor metastasis: The mechanisms and future perspectives.iScience · 2026Review
- Gd-EOB-DTPA-Enhanced Magnetic Resonance Imaging for Predicting Immunotherapy Response in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.Liver cancer · 2026Review
- Recent advances in m6A RNA modification in hepatocellular carcinoma: from mechanisms to therapeutic potential.Frontiers in molecular biosciences · 2026Review
- Single-cell insights into hepatic fibroblasts and stellate cells: heterogeneity in matrix remodelling in development, health, and disease.Npj gut and liver · 2026Review
- Decoding the spatial logic of immune evasion in hepatocellular carcinoma: from single-cell profiling to spatial omics.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
backgroundCancer-associated fibroblasts (CAFs) are key components of the hepatocellular carcinoma (HCC) tumor microenvironment (TME). regulating tumor proliferation, metastasis, therapy resistance, immune evasion via diverse mechanisms. A deeper understanding of the l diversity of CAFs is essential for predicting patient prognosis and guiding treatment strategies.
methodsWe examined the diversity of CAFs in HCC by integrating single-cell, bulk, and spatial transcriptome analyses.
resultsUsing a training cohort of 88 HCC single-cell RNA sequencing (scRNA-seq) samples and a validation cohort of 94 samples, encompassing over 1.2 million cells, we classified three fibroblast subpopulations in HCC: HLA-DRB1 + CAF, MMP11 + CAF, and VEGFA + CAF based on highly expressed genes of which, which are primarily located in normal tissue, tumor boundaries, and tumor interiors, respectively. Cell trajectory analysis revealed that VEGFA + CAFs are at the terminal stage of differentiation, which, notably, is tumor-specific. VEGFA + CAFs were significantly associated with patient survival, and the hypoxic microenvironment was found to be a major factor inducing VEGFA + CAFs. Through cellular communication with capillary endothelial cells (CapECs), VEGFA + CAFs promoted intra-tumoral angiogenesis, facilitating tumor progression and metastasis. Additionally, a machine learning model developed using high-expression genes from VEGFA + CAFs demonstrated high accuracy in predicting prognosis and sorafenib response in HCC patients.
conclusionsWe characterized three fibroblast subpopulations in HCC and revealed their distinct spatial distributions within the tumor. VEGFA + CAFs, which was induced by hypoxic TME, were associated with poorer prognosis, as they promote tumor angiogenesis through cellular communication with CapECs. Our findings provide novel insights and pave the way for individualized therapy in HCC patients.
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