前列腺特异性膜抗原的分子标志在没有治疗的前列腺癌中
Molecular Hallmarks of Prostate-specific Membrane Antigen in Treatment-naïve Prostate Cancer
影响因子:25.20000
分区:医学1区 Top / 泌尿学与肾脏学1区
发表日期:2024 Dec
作者:
Adam B Weiner, Raag Agrawal, Nicholas K Wang, Ida Sonni, Eric V Li, Jaron Arbet, J J H Zhang, James A Proudfoot, Boon Hao Hong, Elai Davicioni, Nathanael Kane, Luca F Valle, Amar U Kishan, Alan Dal Pra, Pirus Ghadjar, Christopher J Sweeney, Nicholas G Nickols, R Jeffrey Karnes, John Shen, Matthew B Rettig, Johannes Czernin, Ashely E Ross, Melvin Lee Kiang Chua, Edward M Schaeffer, Jeremie Calais, Paul C Boutros, Robert E Reiter
摘要
我们表征了肿瘤前列腺特异性膜抗原（PSMA）水平，是癌症生物学和治疗敏感性的反映。我们首先将PSMA Potitron发射断层扫描（PET）最大标准化摄取量（SUVMAX）与肿瘤folH1（PSMA RNA Asna inna As a a Care）相关联。然后，我们在两个大型原发性肿瘤队列中发现并验证了与PSMA RNA水平相关的分子途径。我们验证了独立队列中的这些关联（总计18个； 5684个肿瘤样本），以表征与PSMA的途径和治疗反应。PSMARNA丰度与SUVMAX中等相关（ρ= 0.41）。在独立的队列中，雄激素受体信号在具有较高PSMA的肿瘤中更为活跃。因此，使用雄激素剥夺疗法治疗生化复发（调整后的危害比[AHR] 0.54 [0.34-0.87]; n = 174）时，患有高PSMA肿瘤患者的癌症特异性生存期更长。 PSMA低肿瘤具有对放射疗法的抗性分子标记。与此相一致的是，较高的PSMA肿瘤患者经历了更长的时间在初级放射疗法后复发（AHR 0.50 [0.28-0.90]； n = 248）。在SAKK09/10试验（n = 224）中，接受打捞放射疗法的高PSMA肿瘤患者在64-GY组中经历了更长的时间（限制的平均生存时间[RMST] +7.60 [0.05-15.16]），但这种效应在70-GY臂中受到了损害（RMST 3.52 [3.5] 3.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33.33 to-3.33.33] to-3.33.33 [3.33]局限性包括使用PSMA RNA作为PET SUVMAX的替代物。未经治疗的前列腺癌中的PSMA水平分化了肿瘤生物学和治疗敏感性。这些结果需要使用宠物指标来验证基于成像的管理决策。
Abstract
We characterized tumor prostate-specific membrane antigen (PSMA) levels as a reflection of cancer biology and treatment sensitivities for treatment-naïve prostate cancer.We first correlated PSMA positron emission tomography (PET) maximum standardized uptake values (SUVmax) in primary prostate cancer with tumor FOLH1 (PSMA RNA abundance) to establish RNA as a proxy (n = 55). We then discovered and validated molecular pathways associated with PSMA RNA levels in two large primary tumor cohorts. We validated those associations in independent cohorts (18 total; 5684 tumor samples) to characterize the pathways and treatment responses associated with PSMA.PSMA RNA abundance correlates moderately with SUVmax (ρ = 0.41). In independent cohorts, androgen receptor signaling is more active in tumors with high PSMA. Accordingly, patients with high PSMA tumors experienced longer cancer-specific survival when managed with androgen deprivation therapy for biochemical recurrence (adjusted hazard ratio [AHR] 0.54 [0.34-0.87]; n = 174). PSMA low tumors possess molecular markers of resistance to radiotherapy. Consistent with this, patients with high PSMA tumors experience longer time to recurrence following primary radiotherapy (AHR 0.50 [0.28-0.90]; n = 248). In the SAKK09/10 trial (n = 224), patients with high PSMA tumors who were managed with salvage radiotherapy experienced longer time to progression in the 64-Gy arm (restricted mean survival time [RMST] +7.60 [0.05-15.16]), but this effect was mitigated in the 70-Gy arm (RMST 3.52 [-3.30 to 10.33]). Limitations include using PSMA RNA as a surrogate for PET SUVmax.PSMA levels in treatment-naïve prostate cancer differentiate tumor biology and treatment susceptibilities. These results warrant validation using PET metrics to substantiate management decisions based on imaging.