ArticleAnnals of translational medicine2022
Subpopulations of cancer-associated fibroblasts link the prognosis and metabolic features of pancreatic ductal adenocarcinoma.
Article in Annals of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 73 citations in OpenAlex.
- MYCN-driven metabolic remodelling of the tumour microenvironment in neuroblastoma: implications for stromal biology and CAF heterogeneity.Cancer metastasis reviews · 2026Review
- Improving pancreatic adenocarcinoma prognosis models through ligand receptor interactions and histopathological integration.Journal of translational medicine · 2026Article
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- A tumor microenvironment integrated (TMI) staging system for pancreatic ductal adenocarcinoma based on cancer-associated fibroblast and molecular consensus signatures.Discover oncology · 2026Article
- Favorable histo-molecular remodeling of pancreatic ductal adenocarcinoma after neoadjuvant FOLFIRINOX followed by high-dose stereotactic body radiotherapy.British journal of cancer · 2026Article
- Tumorigenesis and Tumor Microenvironment in Lung Cancer.Current issues in molecular biology · 2026Review
- Stromal cells contribute to progression, recurrence, and metastasis in oral squamous cell carcinoma: a call for therapy.Journal of translational medicine · 2026Review
- A Metastasis-competent CAF Subpopulation Defined byRecent patents on anti-cancer drug discovery · 2026Article
- The Spatiotemporal Heterogeneity of Tumor-Associated Stromal Cells: Reprogramming Plasticity to Unlock Precision Cancer Immunotherapy.Cancer communications (London, England) · 2026Review
- Cancer-Associated Fibroblasts: Clinical Applications in Imaging and Therapy.Tomography (Ann Arbor, Mich.) · 2025Review
- Impact of pancreatic proenzymes on pancreatic ductal adenocarcinoma associated fibroblasts.Scientific reports · 2025Article
- Reprogramming oncogenic mitochondria in pancreatic adenocarcinoma through BRD4 inhibition leads to programmed cell death.The Journal of pharmacology and experimental therapeutics · 2025Article
- Identification of cancer-associated fibroblast subpopulation and construction of an immunotherapy signature for gastric cancer.Translational cancer research · 2025Article
- Stromagenesis and cancer-associated fibroblast heterogeneity in primary tumors and metastasis: focus in non-small cell lung cancer.FEBS open bio · 2025Review
- AEBP1 drives fibroblast-mediated T cell dysfunction in tumors.Nature communications · 2025Article
- Cancer-associated fibroblasts in cancer drug resistance and cancer progression: a review.Cell death discovery · 2025Review
- Integrated single-cell and bulk RNA sequencing reveals prognostic and immunotherapy-associated myofibroblastic cancer-associated fibroblast subtypes in head and neck squamous cell carcinoma.Translational cancer research · 2025Article
- Cancer‑associated fibroblasts: a pivotal regulator of tumor microenvironment in the context of radiotherapy.Cell communication and signaling : CCS · 2025Review
- Stroma and lymphocytes identified by deep learning are independent predictors for survival in pancreatic cancer.Scientific reports · 2025Article
- ARP2/3 complex affects myofibroblast differentiation and migration in pancreatic ductal adenocarcinoma.International journal of cancer · 2025Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Cancer-associated fibroblasts (CAFs) are a vital constituent of the tumor microenvironment (TME) and have several activities, but the effect of CAF heterogeneity on the molecular features and clinical outcomes of pancreatic ductal adenocarcinoma (PDAC) remains unknown. Methods: An algorithm "scFrac" based on single-cell sequencing data from the Gene Expression Omnibus was introduced to emulate the enrichment of CAF subtypes in a TCGA-PDAC cohort and their prognostic influence, and confirmed by an external validation group (66 patients with PDAC) with multiplex immunohistochemistry staining. A comprehensive analysis including metabolic profile and transcription factor regulon activity was carried out among CAF subtypes. Results: Three distinct CAF populations were confirmed: myofibroblast (myCAF), inflammatory CAF (iCAF), and antigen-presenting CAF (apCAF). These subtypes expressed distinct metabolic profiles and transcriptional regulon activity. KEGG pathway annotation demonstrated that complement and coagulation cascades, as well as cytokine-cytokine receptor interaction were dominant in iCAFs, and pathways related to focal adhesion, and ECM-receptor interaction showed dominance in myCAFs, while antigen processing and presentation were the top enriched pathways in apCAFs. iCAFs trended to glycolysis with CREB3L1, EGR2 and SOX4 activation, whereas myCAFs depend on the tricarboxylic acid cycle and its derivatives with NRF2, CEBPD and YBX1 activation. iCAF is a protective factor associated with an inflammatory phenotype, but myCAF is an important factor in the poor prognosis of PDAC. Conclusions: We identified distinct molecular characteristics of 3 CAF subtypes in PDAC and plotted their metabolism profile. We introduced a novel algorism, scFrac, for exploring how CAF subgroups dysregulate cancer biology, and also shed a new therapeutic light on targeting the CAF subtype in TME.
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