Abstract：
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.
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.
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).
FAP expression may serve as a valuable NE marker indicating a worse prognosis in patients with metastatic CRPC.
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.
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).
FAP expression may serve as a valuable NE marker indicating a worse prognosis in patients with metastatic CRPC.
摘要：
晚期前列腺癌（PC）可能会积累基因组改变，这些改变标志着谱系可塑性和转分化为神经内分泌（NE）表型。成纤维细胞活化蛋白（FAP）是上皮-间质转化（EMT）的关键参与者。然而,其在晚期PC中NE分化中的临床价值和作用尚未得到充分研究。
来自多中心的两百八个病人,转移性去势抵抗性前列腺癌（CRPC）患者的前瞻性队列与可用的RNA测序数据分析肿瘤FAPmRNA表达，并研究了其与总生存期（OS）和NE肿瘤特征的关系。
发现21名患者（10％）具有高FAPmRNA表达。与其他相比，该子集对紫杉烷类和AR信号抑制剂（阿比特龙或恩扎鲁他胺）的暴露比例更高，其特征是活跃的NE信号，高NEPC-和低AR-基因表达得分证明。与未改变FAP表达的患者相比，这些具有高FAPmRNA表达的患者具有更积极的临床病程和明显更短的生存期（12个月）（28个月，对数秩p=0.016)。
FAP表达可作为有价值的NE标志物，表明转移性CRPC患者的预后较差。
来自多中心的两百八个病人,转移性去势抵抗性前列腺癌（CRPC）患者的前瞻性队列与可用的RNA测序数据分析肿瘤FAPmRNA表达，并研究了其与总生存期（OS）和NE肿瘤特征的关系。
发现21名患者（10％）具有高FAPmRNA表达。与其他相比，该子集对紫杉烷类和AR信号抑制剂（阿比特龙或恩扎鲁他胺）的暴露比例更高，其特征是活跃的NE信号，高NEPC-和低AR-基因表达得分证明。与未改变FAP表达的患者相比，这些具有高FAPmRNA表达的患者具有更积极的临床病程和明显更短的生存期（12个月）（28个月，对数秩p=0.016)。
FAP表达可作为有价值的NE标志物，表明转移性CRPC患者的预后较差。
