ArticleJournal of translational medicine2025
Tumor-associated-fibrosis and active collagen-CD44 axis characterize a poor-prognosis subtype of gastric cancer and contribute to tumor immunosuppression.
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 35 papers, 2 of them syntheses that pooled it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Impact of metastatic pattern and histologic subtype on PD-(L)1 inhibitor efficacy in HER2-negative advanced gastric and gastroesophageal cancer: a meta-analysis.Frontiers in oncology · 2026Pooled it
- Collagenase-mediated extracellular matrix targeting for enhanced drug penetration and therapeutic efficacy in nanoscale delivery systems for cancer therapy.Journal of nanobiotechnology · 2025Pooled it
- Molecular classification and precision therapy in gastric cancer: Current advances and future perspectives (Review).Oncology reports · 2026Review
- Multi-Tissue Crosstalk Regulating Meniscus Healing Under Inflammation and Physiological Loading.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pharmacogenomic characterization of a uric acid metabolism-related signature associated with prognosis and drug sensitivity in gastric cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Review
- Patient-derived model capturing hypoxia and extracellular matrix remodelling of immunologically cold high-grade serous tumours.Nature communications · 2026Article
- Immunomodulation by collagen VI across fibrotic and tumor microenvironmental contexts.Histology and histopathology · 2026Review
- Review
- Dual-energy computed tomography-derived extracellular volume fraction and spectral quantitative parameters for predicting early recurrence after gastrectomy: insights from a multicenter study.Abdominal radiology (New York) · 2026Article
- Integrative single-cell and bulk transcriptomics define cell death patterns and ZDHHC22 in gastric cancer progression.BMC medical genomics · 2026Article
- Review
- Naringenin, a Food-Derived Flavanone, Suppresses ITGA11-Associated Gastric Cancer Progression via the FAK/PI3K/AKT/mTOR Axis.Cancers · 2026Article
- Review
- Chemoradiation Reprograms Tumor Cells and the Immune Microenvironment in Cervical Cancer.Cancer research · 2026Article
- Single-cell and bulk transcriptomic analyses uncover immune subtypes associated with programmed cell death features in intrahepatic cholangiocarcinoma.Scientific reports · 2026Article
- Tumor microenvironment dynamics in gastric cancer pathogenesis and therapeutic resistance.Molecular cancer · 2026Review
- CD44 upregulation in chronic liver disease marks the transition to hepatocellular carcinoma and portends poor prognosis.British journal of cancer · 2026Article
- Spatial immune niches in gastric cancer immunotherapy resistance: mechanisms and translational implications.Frontiers in immunology · 2026Review
- Electrospun nanofibers for gastric cancer: local therapeutics, biomimetic models, and diagnostic interfaces.Frontiers in oncology · 2026Review
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8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor-associated fibrosis modifies the tumor microenvironment (TME), hinders the infiltration and activity of cytotoxic immune cells, and is a critical pathological process leading to the ineffectiveness of tumor immunotherapy in gastric cancer (GC). However, the specific mechanisms and interventions are yet to be fully explored.
methodsOur study included 375 gastric cancer samples from TCGA, 1 single-cell RNA sequencing (scRNA-seq) dataset comprising of 15 gastric cancer samples from GEO, 19 cohorts of immunotherapy and 2 GWAS datasets. Consensus clustering identified a gastric cancer subtype characterized primarily by fibrosis, and various methods such as pseudotime analysis, CellChat analysis and Colocalization analysis were used to explore its mechanisms.
resultsA subtype of gastric cancer was identified with poor prognosis, characterized by higher malignancy, drug resistance, and poor immune infiltration, associated with elevated expression of genes related with Extracellular matrix (ECM). Single-cell transcriptome analysis showed active Collagen-CD44 signaling axis between cancer-associated fibroblasts (CAFs) and immune cells in gastric cancer, with ECM-related genes upregulated during tumor progression. The expression of CD44 was significantly elevated in the subtype, associated with poor prognosis and tumor immune suppression in gastric cancer, potentially involved in the recruitment of immunosuppressive cells such as M2 macrophages and regulatory T cells (Tregs) and the upregulation of multiple immune checkpoints including PD-1/PD-L1.
conclusionOur study identified a new subtype of gastric cancer, revealing that fibrosis is a critical mechanism driving immune suppression in gastric cancer and emphasizing the central role of the Collagen-CD44 signaling axis. The Collagen-CD44 signaling axis has the potential to serve as a novel therapeutic target for gastric cancer by enhancing immune cell-mediated tumor suppression. By combining it with immune checkpoint inhibitors (ICIs), it may improve the efficacy of immunotherapy for gastric cancer and offer new hope for treatment.
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