Cancer Immunology and Immunotherapy Center, Cancer Research Center, Saint Savas Cancer Hospital, 171 Alexandras Avenue, 11522 Athens, Greece.
Int J Mol Sci. 2023 Sep 22;24(19):14454. doi: 10.3390/ijms241914454.
Recently, we have shown that HLA-A02:01 and HLA-A24:02 in de novo metastatic prostate cancer (MPCa) have an important role in disease progression. Since de novo MPCa represents a small group among patients diagnosed with prostate cancer (PCa), it was obvious to try to extend the validity of our results to larger cohorts of PCa patients. Herein, we analyzed patients irrespective of their disease status at diagnosis to include, besides patients with MPCa, those with localized PCa (LPCa). Our goal was to specify the prognostic value of HLA-A02:01 and HLA-A24:02 for overall survival (OS) prospectively and for early biochemical recurrence (BCR) and castrate resistance (CR) as additional clinical endpoints in a prospective/retrospective manner, to improve clinical decisions for patients covering all stages of PCa. On univariate analysis, HLA-A alleles were significantly associated as prognostic biomarkers with early BCR ( = 0.028; HR = 1.822), OS ( = 0.013; HR = 1.547) and showed a trend for CR ( = 0.150; HR = 1.239). On multivariate analysis, HLA-A alleles proved to be independent prognosticators for early BCR ( = 0.017; HR = 2.008), CR ( = 0.005; HR = 1.615), and OS ( = 0.002; HR = 2.063). Kaplan-Meier analyses revealed that patients belonging to the HLA-A02:01HLA-A24:02 group progressed much faster to BCR and CR and had also shorter OS compared to HLA-A24:02 patients. Patients being HLA-A02:01HLA-A*24:02 exhibited varying clinical outcomes, pointing to the presence of additional HLA-A alleles with potential prognostic value. Our data underline the HLA-A alleles as valuable prognostic biomarkers for PCa that may assist with the appropriate treatment and follow-up schedule based on the risk for disease progression to avoid over-diagnosis and over-treatment.
最近，我们已经证明 HLA-A02:01 和 HLA-A24:02 在新发转移性前列腺癌（MPCa）中对疾病进展起着重要作用。由于新发 MPCa 在被诊断为前列腺癌（PCa）的患者中只占一小部分，因此我们显然试图将我们的结果的有效性扩展到更大的 PCa 患者队列中。在这里，我们分析了无论患者在诊断时的疾病状态如何的患者，包括 MPCa 患者和局限性前列腺癌（LPCa）患者。我们的目标是前瞻性地确定 HLA-A02:01 和 HLA-A24:02 对总生存（OS）的预后价值，并作为额外的临床终点，前瞻性/回顾性地确定早期生化复发（BCR）和去势抵抗（CR），以改善涵盖 PCa 所有阶段的患者的临床决策。单因素分析表明，HLA-A 等位基因作为预测生物标志物与早期 BCR（ = 0.028；HR = 1.822）、OS（ = 0.013；HR = 1.547）显著相关，并显示出 CR 的趋势（ = 0.150；HR = 1.239）。多因素分析表明，HLA-A 等位基因是早期 BCR（ = 0.017；HR = 2.008）、CR（ = 0.005；HR = 1.615）和 OS（ = 0.002；HR = 2.063）的独立预后因素。Kaplan-Meier 分析表明，属于 HLA-A02:01HLA-A24:02 组的患者进展为 BCR 和 CR 的速度更快，OS 也更短，与 HLA-A24:02 患者相比。属于 HLA-A02:01HLA-A*24:02 的患者表现出不同的临床结局，表明存在具有潜在预后价值的其他 HLA-A 等位基因。我们的数据强调了 HLA-A 等位基因作为有价值的 PCa 预后生物标志物，可根据疾病进展的风险，帮助制定适当的治疗和随访计划，以避免过度诊断和过度治疗。
