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image of A Metastasis-competent CAF Subpopulation Defined by MFAP5+THY1+ Co-expression Drives Prostate Cancer Metastasis via EMT Activation

Abstract

Background

The tumor microenvironment, particularly cancer-associated fibroblasts (CAFs), contributes to prostate cancer (PCa) metastasis, however, the role of CAF heterogeneity remains incompletely characterized. The study aims to identify and functionally characterize a metastasis-competent CAF subpopulation in PCa and evaluate its potential as a biomarker for predicting metastatic progression.

Methods

We integrated single-cell RNA sequencing data from 1,214 CAFs across 14 PCa specimens. Metastasis-derived CAFs were functionally validated . Stromal marker expression was assessed by multiplex immunofluorescence in 78 PCa tissues samples.

Results

A 20-gene signature stratified CAFs into three subsets, with the -expressing subset (CAFa) enriched in metastatic patients. Co-expression of and specifically identified CAFa with 96.2% specificity. MFAP5 secretion was associated with AKT phosphorylation, Slug upregulation, and epithelial-mesenchymal transition (EMT). Stromal ++ co-localization predicted postoperative metastasis risk independently of Gleason score (multivariate HR = 5.69, < 0.001).

Discussion

Our findings establish stromal ++ co-localization as a potential prognostic biomarker that could complement Gleason scoring. Further validation in multi-center cohorts is required to confirm its clinical independence.

Conclusion

We identified a metastasis-competent CAF subpopulation defined by ++ co-expression, where serves as a spatial anchor for MFAP5 detection and MFAP5 secretion is functionally linked to AKT/EMT pathway activation.

© 2025 Bentham Science Publishers
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2025-11-26
2026-02-26

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A Metastasis-competent CAF Subpopulation Defined by MFAP5+THY1+ Co-expression Drives Prostate Cancer Metastasis via EMT Activation
Bentham Science Publishers ; https://doi.org/10.2174/0115748928439833251118072935
/content/journals/pra/10.2174/0115748928439833251118072935
/content/journals/pra/10.2174/0115748928439833251118072935
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  • Article Type:     Research Article
Keywords: cancer-associated fibroblasts ; prognostic biomarker ; MFAP5 ; metastasis ; Prostate cancer ; epithelial-mesenchymal transition

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