ArticleJournal of experimental & clinical cancer research : CR2025
Identification and characterization of tumor and stromal derived liquid biopsy analytes in pancreatic ductal adenocarcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Biomarker-Driven Strategies for Stromal Reprogramming in Pancreatic Ductal Adenocarcinoma.Cells · 2026Review
- Review
- Cancer-associated fibroblasts as a critical driver in tumor metastasis: The mechanisms and future perspectives.iScience · 2026Review
- Detection and prognostic role of circulating cancer-associated fibroblasts in the blood of melanoma patients.Frontiers in cell and developmental biology · 2026Article
- Combined action of suicide gene exosomes from pancreatic cancer-associated fibroblasts and from mesenchymal stem cells as a pancreatic ductal adenocarcinoma treatment approach.Cancer cell international · 2025Article
- Multiscale tumor characterization in histopathology via self-distilled transformers and topology-aware visual encoding.Scientific reports · 2025Article
- Cancer-associated fibroblasts as a potential novel liquid biopsy marker in cancer patients.Journal of experimental & clinical cancer research : CR · 2025Review
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22 authors.
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Abstract
backgroundThe lack of predictive biomarkers contributes notably to the poor outcomes of patients with pancreatic ductal adenocarcinoma (PDAC). Cancer-associated fibroblasts (CAFs) are the key components of the prominent PDAC stroma. Data on clinical relevance of CAFs entering the bloodstream, known as circulating CAFs (cCAFs) are scarce. Here, we developed a combined liquid biopsy assay to detect cCAFs and circulating tumor cells (CTCs) in metastatic PDAC (mPDAC) and other metastatic gastrointestinal malignancies (mGI). In addition, we evaluated plasma hyaluronan (HA) levels as a complementary surrogate biomarker of the stromal extent in patients with PDAC.
methodsA sequential liquid biopsy assay based on a two step-enrichment, combining marker dependent and independent cell enrichment, was established for cCAF and CTC detection and validated in mPDAC and mGI patients. The enriched cells were identified by multiplex immunofluorescence. HA measurement was performed by ELISA on blood samples from healthy blood donors (HD), localized and late-stage PDAC patients.
resultscCAFs (≥ 1cCAFs/7.5 mL blood) were detected in 95.4% of mPDAC and in 78.2% of mGI patients, with significantly higher numbers in mPDAC compared to mGI patients (mean number 22.7 vs. 11.0; P = 0.0318). mPDAC patients with ≥ 15 cCAFs/7.5 mL blood had a significant shorter median overall survival (mOS 3.2 months (95% confidence interval (CI) 0.801-5.855) vs. 14.2 months (95% CI 6.055-22.332); P = 0.013), whereby CTC levels were not associated with mOS. In mGI neither cCAFs nor CTCs had a significant impact on OS. HA plasma levels in mPDAC patients were significantly higher compared to HD (mean 123.0 ng/mL vs. 74.45 ng/mL, P = 0.015). High HA in localized and late-stage PDAC were associated with a significantly shorter mOS (mOS
conclusionsOur liquid biopsy assay provides robust detection of cCAFs in mPDAC and mGI patients. The measurement of both circulatory stromal parameters, cCAFs and HA, adds valuable clinical information as they are associated with an unfavorable outcome in PDAC. These results highlight that stromal characteristics unique to PDAC could be leveraged to fill the current gap in discovering predictive biomarkers.
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