Prostate-specific membrane antigen (PSMA) is frequently overexpressed in nonprostate malignancies. This preclinical study investigated the molecular basis of the application of PMSA-targeting radiopharmaceuticals in breast cancer subtypes. Methods: The somatic copy number status and the transcriptomic and protein expressions of FOLH1 (gene name of PSMA) were analyzed across breast cancer subtypes in 998 patients from The Cancer Genome Atlas dataset. Results: FOLH1 was frequently amplified in basallike breast cancer (BLBC) (32%) compared with luminal and human epidermal growth factor receptor 2–positive subtypes (16% and 17%, respectively; P < 0.01). FOLH1 expression was higher in BLBC (P < 0.001) and was negatively correlated with estrogen-receptor and progesterone-receptor expressions. Consistently, the PSMA protein level was higher in BLBC (P < 0.05). Interestingly, FOLH1 expression was associated with relapse-free and distant metastasis–free survival in patients with BLBC. Conclusion: The BLBC subtype exhibited frequent amplification and overexpression of PSMA, supporting the exploration of PSMA-targeting radiopharmaceuticals in this aggressive breast cancer subtype.

前列腺特异性膜抗原（PSMA）在非前列腺恶性肿瘤中经常过度表达。这项临床前研究调查了 PMSA 靶向放射性药物在乳腺癌亚型中应用的分子基础。方法：对来自癌症基因组图谱数据集的 998 名乳腺癌亚型患者的体细胞拷贝数状态以及FOLH1 （PSMA 的基因名称）的转录组和蛋白表达进行分析。结果：与管腔和人表皮生长因子受体 2 阳性亚型（分别为 16% 和 17%； P < 0.01）相比， FOLH1在基底样乳腺癌 (BLBC) 中频繁扩增（32%）。 FOLH1在 BLBC 中表达较高（ P < 0.001），并且与雌激素受体和孕激素受体表达呈负相关。一致地，BLBC 中的 PSMA 蛋白水平较高（ P < 0.05）。有趣的是， FOLH1表达与 BLBC 患者的无复发和无远处转移生存相关。结论： BLBC 亚型表现出 PSMA 的频繁扩增和过度表达，支持在这种侵袭性乳腺癌亚型中探索 PSMA 靶向放射性药物。