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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774973/ https://www.ncbi.nlm.nih.gov/pubmed/35052475 http://dx.doi.org/10.3390/genes13010135 |
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author | Vlachostergios, Panagiotis J. Karathanasis, Athanasios Tzortzis, Vassilios |
author_facet | Vlachostergios, Panagiotis J. Karathanasis, Athanasios Tzortzis, Vassilios |
author_sort | Vlachostergios, Panagiotis J. |
collection | PubMed |
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 FAP 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 FAP 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 FAP expression had a more aggressive clinical course and significantly shorter survival (12 months) compared to those without altered FAP expression (28 months, log-rank p = 0.016). Conclusions: FAP expression may serve as a valuable NE marker indicating a worse prognosis in patients with metastatic CRPC. |
format | Online Article Text |
id | pubmed-8774973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87749732022-01-21 Expression of Fibroblast Activation Protein Is Enriched in Neuroendocrine Prostate Cancer and Predicts Worse Survival Vlachostergios, Panagiotis J. Karathanasis, Athanasios Tzortzis, Vassilios Genes (Basel) Article 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 FAP 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 FAP 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 FAP expression had a more aggressive clinical course and significantly shorter survival (12 months) compared to those without altered FAP expression (28 months, log-rank p = 0.016). Conclusions: FAP expression may serve as a valuable NE marker indicating a worse prognosis in patients with metastatic CRPC. MDPI 2022-01-13 /pmc/articles/PMC8774973/ /pubmed/35052475 http://dx.doi.org/10.3390/genes13010135 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Vlachostergios, Panagiotis J. Karathanasis, Athanasios Tzortzis, Vassilios Expression of Fibroblast Activation Protein Is Enriched in Neuroendocrine Prostate Cancer and Predicts Worse Survival |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774973/ https://www.ncbi.nlm.nih.gov/pubmed/35052475 http://dx.doi.org/10.3390/genes13010135 |
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