Homeobox 13 (HOXB13) is an oncogenic transcription factor that directly regulates expression of folate hydrolase 1, which encodes prostate-specific membrane antigen (PSMA). HOXB13 is expressed in primary and metastatic prostate cancers (PCs) and promotes androgen-independent PC growth. Since HOXB13 promotes resistance to androgen receptor (AR)–targeted therapies and regulates the expression of folate hydrolase 1, we investigated whether SUVs on PSMA PET would correlate with HOXB13 expression. Methods: We analyzed 2 independent PC patient cohorts who underwent PSMA PET/CT for initial staging or for biochemical recurrence. In the discovery cohort, we examined the relationship between HOXB13, PSMA, and AR messenger RNA (mRNA) expression in prostate biopsy specimens from 179 patients who underwent PSMA PET/CT with ¹⁸F-piflufolastat. In the validation cohort, we confirmed the relationship between HOXB13, PSMA, and AR by comparing protein expression in prostatectomy and lymph node (LN) sections from 19 patients enrolled in ¹⁸F-rhPSMA-7.3 PET clinical trials. Correlation and association analyses were also used to confirm the relationship between the markers, LN positivity, and PSMA PET SUVs. Results: We observed a significant correlation between PSMA and HOXB13 mRNA (P < 0.01). The association between HOXB13 and ¹⁸F-piflufolastat SUVs was also significant (SUV_max, P = 0.0005; SUV_peak, P = 0.0006). Likewise, the PSMA SUV_max was significantly associated with the expression of HOXB13 protein in the ¹⁸F-rhPSMA-7.3 PET cohort (P = 0.008). Treatment-naïve patients with LN metastases demonstrated elevated HOXB13 and PSMA levels in their tumors as well as higher PSMA tracer uptake and low AR expression. Conclusion: Our findings demonstrate that HOXB13 correlates with PSMA expression and PSMA PET SUVs at the mRNA and protein levels. Our study suggests that the PSMA PET findings may reflect oncogenic HOXB13 transcriptional activity in PC, thus potentially serving as an imaging biomarker for more aggressive disease.

同源盒 13 (HOXB13) 是一种致癌转录因子，可直接调节叶酸水解酶 1 的表达，叶酸水解酶 1 编码前列腺特异性膜抗原 (PSMA)。 HOXB13 在原发性和转移性前列腺癌 (PC) 中表达，并促进不依赖雄激素的 PC 生长。由于 HOXB13 促进对雄激素受体 (AR) 靶向治疗的耐药性并调节叶酸水解酶 1 的表达，因此我们研究了 PSMA PET 上的 SUV 是否与 HOXB13 表达相关。方法：我们分析了 2 个独立的 PC 患者队列，他们接受了 PSMA PET/CT 进行初始分期或生化复发。在发现队列中，我们检查了 179 名患者的前列腺活检标本中 HOXB13、PSMA 和 AR 信使 RNA (mRNA) 表达之间的关系，这些患者接受了¹⁸ F-piflufolastat 的 PSMA PET/CT。在验证队列中，我们通过比较参加^{18 项}F-rhPSMA-7.3 PET 临床试验的 19 名患者的前列腺切除术和淋巴结 (LN) 切片中的蛋白表达，证实了 HOXB13、PSMA 和 AR 之间的关系。还使用相关性和关联分析来确认标记物、LN 阳性和 PSMA PET SUV 之间的关系。结果：我们观察到 PSMA 和 HOXB13 mRNA 之间存在显着相关性（ P < 0.01）。 HOXB13 和¹⁸ F-piflufolastat SUV 之间的关联也很显着（SUV _max ， P = 0.0005；SUV _Peak ， P = 0.0006）。同样，PSMA SUV _max与¹⁸ F-rhPSMA-7.3 PET 队列中 HOXB13 蛋白的表达显着相关（ P = 0.008）。 初治的淋巴结转移患者表现出肿瘤中 HOXB13 和 PSMA 水平升高，以及 PSMA 示踪剂摄取较高和 AR 表达较低。结论：我们的研究结果表明，HOXB13 在 mRNA 和蛋白质水平上与 PSMA 表达和 PSMA PET SUV 相关。我们的研究表明，PSMA PET 结果可能反映了 PC 中的致癌 HOXB13 转录活性，因此有可能作为更具侵袭性疾病的成像生物标志物。