ArticleJournal of translational medicine2025
Single-cell and spatial-resolved profiling reveals cancer-associated fibroblast heterogeneity in colorectal cancer metabolic subtypes.
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 23 papers.
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Who cites it
23 citing papers in PubMed.
- The Single-Cell and Spatial Transcriptomics Atlas of Epithelial-Fibroblast Interactions in Colorectal Cancer.Digestive diseases and sciences · 2026Article
- Targeting colorectal cancer and T‑cell metabolism for the treatment of colorectal cancer (Review).Oncology reports · 2026Review
- Integrative single-cell and multi-omics analysis of ZBTB21-mediated serine metabolism in colorectal cancer: from metabolic reprogramming to immune microenvironment modulation.Cancer immunology, immunotherapy : CII · 2026Article
- Article
- Research on the Hippo Pathway in Cancer.Cells · 2026Review
- Decoding the CAF-TAM axis: multi-omics dissection and therapeutic targeting of stromal-immune crosstalk in the tumor microenvironment.Cell death & disease · 2026Review
- Targeting phase separation: a new strategy to disrupt the stromal-immune axis in colorectal cancer.Cell communication and signaling : CCS · 2026Review
- Integrated single-cell and spatial transcriptomic analysis reveals mCAF-SPP1⁺ macrophage-T cell crosstalk shaping immunosuppressive niches in colorectal cancer liver metastasis.Journal of translational medicine · 2026Article
- The distinct roles of ROS in tumor immunity: from mechanisms to immunotherapeutic applications.Journal of hematology & oncology · 2026Review
- Comprehensive pan-cancer analysis reveals SH3GLB1 is a novel prognostic biomarker with immunomodulatory potential.Biology direct · 2026Article
- Single-cell RNA sequencing unveils enhanced antitumor immunity in colorectal cancer with PD-1 blockade and LINC00673 deletion.Biomarker research · 2026Article
- The tumor immune microenvironment of thyroid cancer and colorectal cancer: cellular crosstalk and therapeutic implications.Frontiers in immunology · 2026Review
- Dissecting tumor heterogeneity in colorectal cancer: uncovering the role of BCL2L1Frontiers in immunology · 2026Article
- Phenotypic and ultrastructural heterogeneity of fibroblasts and vasculogenic mimicry in rectal adenocarcinoma following neoadjuvant chemoradiotherapy.Histochemistry and cell biology · 2025Article
- DAGFormer: A graph-based domain adaptation approach for single-cell cancer drug response prediction.PLoS computational biology · 2025Article
- Dynamic remodelling of epithelial plasticity in colorectal cancer from single-cell and spatially resolved perspectives.Journal of translational medicine · 2025Article
- Cancer-Associated Fibroblasts: Origin, Classification, Tumorigenicity, and Targeting for Cancer Therapy.MedComm · 2025Review
- Crosstalk Between Metabolic Reprogramming and Epigenetic Modifications in Colorectal Cancer: Mechanisms and Clinical Applications.Current issues in molecular biology · 2025Review
- Different metabolic paradigms and distribution of regulatory T cells between primary and lymph node metastasis prostate cancer.CytoJournal · 2025Article
- Cancer-associated fibroblasts: dual roles from senescence sentinels to death regulators and new dimensions in therapy.Frontiers in immunology · 2025Review
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Authors and funding
12 authors.
Funding
Abstract
backgroundColorectal cancer (CRC) presents significant treatment challenges due to its high heterogeneity and complex intercellular interactions. Further exploration of CRC subtypes and interactions among tumor-specific clusters will facilitate the development of personalized treatment strategies.
methodsSingle-cell RNA sequencing and bulk RNA sequencing datasets were integrated to determine CRC metabolic subtypes by hierarchical clustering. The analysis was further extended to cellchat, pseudotime, immune infiltration, and clinicopathological relevance to explore the characteristics of secreted frizzled related protein 2 (SFRP2) + cancer-associated fibroblast (CAF) clusters, and validated by spatial transcriptomics (ST), in vivo experiments, and multiple immunohistochemistry (mIHC).
resultsCRC samples were stably classified into three heterogeneous metabolic subtypes, each exhibiting different microenvironment and CAF heterogeneity, particularly in the distribution of SFRP2 + CAF, which was aligned with metabolic activity. SFRP2 + CAF exhibits high extracellular matrix (ECM) activity and is closely involved in cellular communication, not only promoting the malignant progression of cancer cells but also inducing the differentiation of Tregs. Compared to responders of chemotherapy, the proportion of SFRP2 + CAFs is significantly increased in non-responders. Importantly, mIHC and ST analyses confirm that cancer cells with low expression of agmatinase (AGMAT) can recruit SFRP2 + CAFs, and Treg infiltration surrounding SFRP2 + CAFs was observed. AGMAT combined with oxaliplatin showed the best efficacy in vivo, which may be associated with the inhibition of SFRP2 + CAF infiltration.
conclusionsOur study identified and described the potential protumor biological properties of SFRP2 + CAFs, and AGMAT may be a valuable target for disrupting their properties.
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