Cancer‐associated fibroblast subtypes in the tumor microenvironment of prostate cancer and associations to patient outcomes
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2026
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| author | Marcus Lunau Blanke Paul Vinu Salachan Jeanette Bæhr Georgsen Jacob Fredsøe Benedicte Ulhøi Michael Borre Karina D. Sørensen |
| author_facet | Marcus Lunau Blanke Paul Vinu Salachan Jeanette Bæhr Georgsen Jacob Fredsøe Benedicte Ulhøi Michael Borre Karina D. Sørensen Marcus Lunau Blanke Paul Vinu Salachan Jeanette Bæhr Georgsen Jacob Fredsøe Benedicte Ulhøi Michael Borre Karina D. Sørensen |
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| contents | Cancer‐associated fibroblast subtypes in the tumor microenvironment of prostate cancer and associations to patient outcomes Marcus Lunau Blanke Paul Vinu Salachan Jeanette Bæhr Georgsen Jacob Fredsøe Benedicte Ulhøi Michael Borre Karina D. Sørensen The Journal of Pathology Abstract Prostate cancer (PC) is a prevalent malignancy, and outcomes range from indolent disease to terminal illness. Prostate‐specific antigen‐based diagnostics lack specificity and correlation with tumor aggressiveness, leading to overdiagnosis and undertreatment. Recent studies on cancer‐associated fibroblasts (CAFs) have identified antigen presenting CAFs (apCAF), inflammatory CAFs (iCAF), and myofibrillar CAFs (myCAF) in pancreatic ductal adenocarcinoma, non‐small‐cell lung cancer, and breast cancer. However, their significance in PC is not yet understood. This study employs publicly available single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics (ST) data combined with multiplex immunofluorescence (mIF) and digital pathology analyses of radical prostatectomy (RP) specimens from two cohorts (cohort 1, n = 235; cohort 2, n = 240) to identify CAF subtypes in localized PC and their association with biochemical recurrence (BCR) by uni‐ and multivariable [adjusted for Cancer of the Prostate Risk Assessment postsurgical (CAPRA‐S) score] Cox regression analyses. We identified myCAFs, iCAFs, and apCAFs in PC by analyzing scRNA‐seq and ST data. We also identified the three CAF subtypes by mIF staining of RP specimens from cohorts 1 and 2. In prostate tumors, higher numbers of apCAFs and myCAFs were present close to malignant versus adjacent nonmalignant (AN) glands ( p < 0.001, Wilcoxon test), whereas we saw no significant difference for iCAFs. In univariable Cox regression analyses, high levels of apCAFs and iCAFs were associated with increased risk of BCR in cohort 1 [apCAF: hazard ratio (HR): 1,78, p < 0.05, iCAF: HR: 1,76, p < 0.05] and confirmed in cohort 2 (apCAF: HR: 1.85, p < 0.05, iCAF: HR: 2.06, p < 0.05). In multivariable Cox regression analyses, both apCAF and iCAF levels remained independently associated with BCR after adjustment for CAPRA‐S score. Our findings imply the potential of CAF subtypes as biomarkers for risk stratification in PC. © 2026 The Pathological Society of Great Britain and Ireland. 10.1002/path.70023 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/path.70023 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_path_70023 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2026 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Cancer‐associated fibroblast subtypes in the tumor microenvironment of prostate cancer and associations to patient outcomes Marcus Lunau Blanke Paul Vinu Salachan Jeanette Bæhr Georgsen Jacob Fredsøe Benedicte Ulhøi Michael Borre Karina D. Sørensen The Journal of Pathology Cancer‐associated fibroblast subtypes in the tumor microenvironment of prostate cancer and associations to patient outcomes Marcus Lunau Blanke Paul Vinu Salachan Jeanette Bæhr Georgsen Jacob Fredsøe Benedicte Ulhøi Michael Borre Karina D. Sørensen The Journal of Pathology Abstract Prostate cancer (PC) is a prevalent malignancy, and outcomes range from indolent disease to terminal illness. Prostate‐specific antigen‐based diagnostics lack specificity and correlation with tumor aggressiveness, leading to overdiagnosis and undertreatment. Recent studies on cancer‐associated fibroblasts (CAFs) have identified antigen presenting CAFs (apCAF), inflammatory CAFs (iCAF), and myofibrillar CAFs (myCAF) in pancreatic ductal adenocarcinoma, non‐small‐cell lung cancer, and breast cancer. However, their significance in PC is not yet understood. This study employs publicly available single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics (ST) data combined with multiplex immunofluorescence (mIF) and digital pathology analyses of radical prostatectomy (RP) specimens from two cohorts (cohort 1, n = 235; cohort 2, n = 240) to identify CAF subtypes in localized PC and their association with biochemical recurrence (BCR) by uni‐ and multivariable [adjusted for Cancer of the Prostate Risk Assessment postsurgical (CAPRA‐S) score] Cox regression analyses. We identified myCAFs, iCAFs, and apCAFs in PC by analyzing scRNA‐seq and ST data. We also identified the three CAF subtypes by mIF staining of RP specimens from cohorts 1 and 2. In prostate tumors, higher numbers of apCAFs and myCAFs were present close to malignant versus adjacent nonmalignant (AN) glands ( p < 0.001, Wilcoxon test), whereas we saw no significant difference for iCAFs. In univariable Cox regression analyses, high levels of apCAFs and iCAFs were associated with increased risk of BCR in cohort 1 [apCAF: hazard ratio (HR): 1,78, p < 0.05, iCAF: HR: 1,76, p < 0.05] and confirmed in cohort 2 (apCAF: HR: 1.85, p < 0.05, iCAF: HR: 2.06, p < 0.05). In multivariable Cox regression analyses, both apCAF and iCAF levels remained independently associated with BCR after adjustment for CAPRA‐S score. Our findings imply the potential of CAF subtypes as biomarkers for risk stratification in PC. © 2026 The Pathological Society of Great Britain and Ireland. 10.1002/path.70023 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Cancer‐associated fibroblast subtypes in the tumor microenvironment of prostate cancer and associations to patient outcomes |
| topic | The Journal of Pathology |
| url | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.70023 |