Purpose: Prostate-specific membrane antigen (PSMA)–based images, which visually quantify PSMA expression, are used to determine prostate cancer micrometastases. This study evaluated whether a circulating tumor cell (CTC)–based transcript platform, including PSMA mRNA, could help identify potential prognostic markers in prostate cancer. Experimental Design: We prospectively enrolled 21 healthy individuals and 247 patients with prostate cancer [localized prostate cancer (LPCa), n = 94; metastatic hormone–sensitive prostate cancer (mHSPC), n = 44; and metastatic castration-resistant prostate cancer (mCRPC), n = 109]. The mRNA expression of six transcripts [PSMA, prostate-specific antigen (PSA), AR, AR-V7, EpCAM, and KRT 19] from CTCs was measured, and their relationship with biochemical recurrence (BCR) in LPCa and mCRPC progression-free survival (PFS) rate in mHSPC was assessed. PSA-PFS and radiological-PFS were also calculated to identify potential biomarkers for predicting androgen receptor signaling inhibitor (ARSI) and taxane-based chemotherapy resistance in mCRPC. Results: CTC detection rates were 75.5%, 95.3%, and 98.0% for LPCa, mHSPC, and mCRPC, respectively. In LPCa, PSMA [hazard ratio (HR), 3.35; P = 0.028) and PSA mRNA (HR, 1.42; P = 0.047] expressions were associated with BCR. Patients with mHSPC with high PSMA (HR, 4.26; P = 0.020) and PSA mRNA (HR, 3.52; P = 0.042) expressions showed significantly worse mCRPC-PFS rates than those with low expression. Increased PSA and PSMA mRNA expressions were significantly associated with shorter PSA-PFS and radiological PFS in mCPRC, indicating an association with drug resistance. Conclusions: PSMA and PSA mRNA expressions are associated with BCR in LPCa. In advanced prostate cancer, PSMA and PSA mRNA can also predict rapid progression from mHSPC to mCRPC and ARSI or taxane-based chemotherapy resistance.

中文翻译：

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循环肿瘤细胞表达的前列腺特异性膜抗原和前列腺特异性抗原转录对前列腺癌不同阶段的影响

目的：基于前列腺特异性膜抗原 (PSMA) 的图像可直观地量化 PSMA 表达，用于确定前列腺癌微转移。这项研究评估了基于循环肿瘤细胞 (CTC) 的转录平台（包括 PSMA mRNA）是否可以帮助识别前列腺癌的潜在预后标志物。实验设计：我们前瞻性地招募了 21 名健康个体和 247 名前列腺癌患者[局限性前列腺癌 (LPCa)，n = 94；转移性激素敏感性前列腺癌 (mHSPC)，n = 44；和转移性去势抵抗性前列腺癌 (mCRPC)，n = 109]。测量了来自 CTC 的六种转录物 [PSMA、前列腺特异性抗原 (PSA)、AR、AR-V7、EpCAM 和 KRT 19] 的 mRNA 表达，及其与 LPCa 和 mCRPC 无进展生化复发 (BCR) 的关系评估了 mHSPC 的生存率 (PFS)。还计算了 PSA-PFS 和放射学 PFS，以确定预测 mCRPC 中雄激素受体信号抑制剂 (ARSI) 和基于紫杉烷的化疗耐药性的潜在生物标志物。结果：LPCa、mHSPC 和 mCRPC 的 CTC 检出率分别为 75.5%、95.3% 和 98.0%。在 LPCa、PSMA 中[风险比 (HR)，3.35； P = 0.028）和 PSA mRNA（HR，1.42；P = 0.047）表达与 BCR 相关。具有高 PSMA（HR，4.26；P = 0.020）和 PSA mRNA（HR，3.52；P = 0.042）表达的 mHSPC 患者PSA 和 PSMA mRNA 表达增加与 mCPRC 中较短的 PSA-PFS 和放射学 PFS 显着相关，表明与耐药性相关。 LPCa 中的 BCR。在晚期前列腺癌中，PSMA 和 PSA mRNA 还可以预测从 mHSPC 到 mCRPC 和 ARSI 或基于紫杉烷的化疗耐药的快速进展。