Prognostic Potential of Cancer-Associated Fibroblast Surface Markers and Their Specific DNA Methylation in Prostate Cancer

<b>Background:</b> Cancer-associated fibroblasts (CAFs) are a key component of the prostate cancer (PCa) microenvironment, the abundance of which is often linked to poor prognosis. The surface markers for CAFs are mostly established, yet our current knowledge of epigenetic alterations in them remains limited. The aim of this study was to evaluate the relationship between CAF-specific DNA methylation, their abundance and the PCa prognosis. <b>Methods:</b> The study included 88 PCa patients with known presence or absence of a biochemical recurrence within a 6-year period. Resected PCa tissue was assessed for the surface expression of FAP, PDGFRb, CD90, and POST, and for the methylation of <i>EDARADD</i>, <i>GATA6</i>, and <i>PITX2</i> genes using qPCR and ddPCR. <b>Results:</b> The surface expression of FAP, PDGFRb and CD90 was associated with a higher Gleason score (<i>p</i> < 0.05). The analytical sensitivity of ddPCR was superior to qPCR; results obtained using ddPCR demonstrated a more significant association with clinical features of PCa. <i>EDARADD</i> methylation and PDGFRb expression were associated with a risk of biochemical recurrence (HR-0.961 [95% CI: 0.931-0.991] and HR-2.313 [95% CI: 1.054-5.088]; <i>p</i> < 0.05, respectively). <b>Conclusions:</b> Upon further validation, the abundance of CAFs and their specific methylation might become a promising tool for the assessment of prognosis in PCa after radical treatment.