Expression of Fibroblast Activation Protein Is Enriched in Neuroendocrine Prostate Cancer and Predicts Worse Survival
Background: Advanced prostate cancer (PC) may accumulate genomic alterations that hallmark lineage plasticity and transdifferentiation to a neuroendocrine (NE) phenotype. Fibroblast activation protein (FAP) is a key player in epithelial-to-mesenchymal transition (EMT). However, its clinical value an...
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| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/1/135 |
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| author | Panagiotis J. Vlachostergios Athanasios Karathanasis Vassilios Tzortzis |
| author_facet | Panagiotis J. Vlachostergios Athanasios Karathanasis Vassilios Tzortzis |
| author_sort | Panagiotis J. Vlachostergios |
| collection | DOAJ |
| description | Background: Advanced prostate cancer (PC) may accumulate genomic alterations that hallmark lineage plasticity and transdifferentiation to a neuroendocrine (NE) phenotype. Fibroblast activation protein (FAP) is a key player in epithelial-to-mesenchymal transition (EMT). However, its clinical value and role in NE differentiation in advanced PC has not been fully investigated. Methods: Two hundred and eight patients from a multicenter, prospective cohort of patients with metastatic castration-resistant prostate cancer (CRPC) with available RNA sequencing data were analyzed for tumor <i>FAP</i> mRNA expression, and its association with overall survival (OS) and NE tumor features was investigated. Results: Twenty-one patients (10%) were found to have high <i>FAP</i> mRNA expression. Compared to the rest, this subset had a proportionally higher exposure to taxanes and AR signaling inhibitors (abiraterone or enzalutamide) and was characterized by active NE signaling, evidenced by high NEPC- and low AR-gene expression scores. These patients with high tumor mRNA <i>FAP</i> expression had a more aggressive clinical course and significantly shorter survival (12 months) compared to those without altered <i>FAP</i> expression (28 months, log-rank <i>p</i> = 0.016). Conclusions: <i>FAP</i> expression may serve as a valuable NE marker indicating a worse prognosis in patients with metastatic CRPC. |
| first_indexed | 2024-03-10T01:25:20Z |
| format | Article |
| id | doaj.art-ec016887367c44ef92966290922af011 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T01:25:20Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-ec016887367c44ef92966290922af0112023-11-23T13:52:55ZengMDPI AGGenes2073-44252022-01-0113113510.3390/genes13010135Expression of Fibroblast Activation Protein Is Enriched in Neuroendocrine Prostate Cancer and Predicts Worse SurvivalPanagiotis J. Vlachostergios0Athanasios Karathanasis1Vassilios Tzortzis2Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USADepartment of Urology, University of Thessaly School of Health Sciences Faculty of Medicine, University Hospital of Larissa, 41100 Larissa, GreeceDepartment of Urology, University of Thessaly School of Health Sciences Faculty of Medicine, University Hospital of Larissa, 41100 Larissa, GreeceBackground: Advanced prostate cancer (PC) may accumulate genomic alterations that hallmark lineage plasticity and transdifferentiation to a neuroendocrine (NE) phenotype. Fibroblast activation protein (FAP) is a key player in epithelial-to-mesenchymal transition (EMT). However, its clinical value and role in NE differentiation in advanced PC has not been fully investigated. Methods: Two hundred and eight patients from a multicenter, prospective cohort of patients with metastatic castration-resistant prostate cancer (CRPC) with available RNA sequencing data were analyzed for tumor <i>FAP</i> mRNA expression, and its association with overall survival (OS) and NE tumor features was investigated. Results: Twenty-one patients (10%) were found to have high <i>FAP</i> mRNA expression. Compared to the rest, this subset had a proportionally higher exposure to taxanes and AR signaling inhibitors (abiraterone or enzalutamide) and was characterized by active NE signaling, evidenced by high NEPC- and low AR-gene expression scores. These patients with high tumor mRNA <i>FAP</i> expression had a more aggressive clinical course and significantly shorter survival (12 months) compared to those without altered <i>FAP</i> expression (28 months, log-rank <i>p</i> = 0.016). Conclusions: <i>FAP</i> expression may serve as a valuable NE marker indicating a worse prognosis in patients with metastatic CRPC.https://www.mdpi.com/2073-4425/13/1/135fibroblast activating proteinneuroendocrine differentiationprostate cancercastration-resistantandrogen receptor |
| spellingShingle | Panagiotis J. Vlachostergios Athanasios Karathanasis Vassilios Tzortzis Expression of Fibroblast Activation Protein Is Enriched in Neuroendocrine Prostate Cancer and Predicts Worse Survival Genes fibroblast activating protein neuroendocrine differentiation prostate cancer castration-resistant androgen receptor |
| title | Expression of Fibroblast Activation Protein Is Enriched in Neuroendocrine Prostate Cancer and Predicts Worse Survival |
| title_full | Expression of Fibroblast Activation Protein Is Enriched in Neuroendocrine Prostate Cancer and Predicts Worse Survival |
| title_fullStr | Expression of Fibroblast Activation Protein Is Enriched in Neuroendocrine Prostate Cancer and Predicts Worse Survival |
| title_full_unstemmed | Expression of Fibroblast Activation Protein Is Enriched in Neuroendocrine Prostate Cancer and Predicts Worse Survival |
| title_short | Expression of Fibroblast Activation Protein Is Enriched in Neuroendocrine Prostate Cancer and Predicts Worse Survival |
| title_sort | expression of fibroblast activation protein is enriched in neuroendocrine prostate cancer and predicts worse survival |
| topic | fibroblast activating protein neuroendocrine differentiation prostate cancer castration-resistant androgen receptor |
| url | https://www.mdpi.com/2073-4425/13/1/135 |
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