Department of Urology, Prof. Doutor Fernando Fonseca Hospital, Amadora, Portugal.
Cancer Biology and Epigenetics Group, Research Center (CI-IPOP), Portuguese Oncology Institute of Porto, Porto, Portugal; Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal; Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal.
Urol Oncol. 2020 Oct;38(10):794.e17-794.e27. doi: 10.1016/j.urolonc.2020.03.004. Epub 2020 Apr 9.
The influence of inflammation on prostate tumor carcinogenesis is currently much better known than with its role in prostate cancer (CaP) progression. We evaluated the prognostic value of epigenetic (HDAC1, HDAC4, H3Ac) and inflammation-related (CXCR4, CXCR7, CXCL12) biomarkers immunoexpression, in radical prostatectomy specimens, from 2 cohorts of CaP patients with long term follow-up.
Formalin-fixed and paraffin-embedded radical prostatectomy specimens were obtained from the pathology archives of Prof. Doutor Fernando Fonseca Hospital, in Amadora, Portugal and Portuguese Oncology Institute of Porto, in Porto, Portugal, and tissue microarrays were assembled. It was achieved a set of 234 patients submitted to radical retropubic prostatectomy between January 2000 and December 2005. Immunohistochemistry was used for evaluation of protein expression of epigenetic and inflammation-related markers. Nuclear staining was assessed using digital image analysis. Study outcomes included disease-specific survival and disease-free survival (DFS). Statistical analysis was tabulated using SPSS version 23.0. Hazard ratios (HRs) and survival curves were estimated using Cox-regression and Kaplan-Meyer models, respectively. Statistical significance was set at P < 0.05.
Complete follow-up data was available for 234 patients and median follow-up time was 164 [11-218] months. Patients with higher CXCR4 immunoexpression experienced significantly worse disease-specific survival compared to patients with low expression (HR = 1.016, 95% CI: 1.002-1.031). The same happened with CXCL12 (HR = 0.546 95% CI: 0.322-0.926) and H3Ac (HR = 1.015, 95% CI: 1.001c1.029). In what concerns to DFS, patients with higher expression of CXCR4 and CXCR7 were significantly more prone to experience disease recurrence (HR = 1.003, 95% CI: 1.000-1.005 and HR = 1.111, 95% CI:1.032-1.196, respectively). When adjusted to pTStage and WHO Grade Groups, CXCR7 maintained independent impact on DFS (HR = 1.119, 95% CI: 1.032-1.214).
The interplay between inflammation and epigenetics and its impact in CaP outcome deserves further studies in the future. CXCR7 shows an independent predictor for worse DFS after radical prostatectomy, and could provide important prognostic information for patient management after radical prostatectomy.
目前，人们对炎症在前列腺肿瘤发生中的影响的了解要优于其在前列腺癌（CaP）进展中的作用。我们评估了 2 组接受根治性前列腺切除术的 CaP 患者长期随访的根治性前列腺切除标本中表观遗传学（HDAC1、HDAC4、H3Ac）和炎症相关（CXCR4、CXCR7、CXCL12）生物标志物免疫表达的预后价值。
从葡萄牙阿马多拉的 Fernando Fonseca 教授医院和葡萄牙波尔图的葡萄牙肿瘤研究所的病理档案中获得了福尔马林固定和石蜡包埋的根治性前列腺切除术标本，并组装了组织微阵列。共获得了 234 名 2000 年 1 月至 2005 年 12 月期间接受根治性耻骨后前列腺切除术的患者的一套数据。使用免疫组织化学评估表观遗传学和炎症相关标志物的蛋白表达。使用数字图像分析评估核染色。研究结果包括疾病特异性生存和无病生存（DFS）。使用 SPSS 版本 23.0 对统计数据进行制表。使用 Cox 回归和 Kaplan-Meier 模型分别估计风险比（HR）和生存曲线。统计学意义设为 P<0.05。
234 名患者均获得完整的随访数据，中位随访时间为 164 [11-218] 个月。与低表达相比，CXCR4 免疫表达较高的患者疾病特异性生存率明显较差（HR=1.016，95%CI：1.002-1.031）。同样的情况也发生在 CXCL12（HR=0.546，95%CI：0.322-0.926）和 H3Ac（HR=1.015，95%CI：1.001c1.029）。在DFS 方面，CXCR4 和 CXCR7 表达较高的患者复发的风险明显更高（HR=1.003，95%CI：1.000-1.005 和 HR=1.111，95%CI：1.032-1.196）。调整 pT 分期和世卫组织分级组后，CXCR7 对 DFS 仍具有独立影响（HR=1.119，95%CI：1.032-1.214）。
炎症与表观遗传学之间的相互作用及其对 CaP 结局的影响值得进一步研究。CXCR7 是根治性前列腺切除术后 DFS 的独立预测因子，可为根治性前列腺切除术后患者的管理提供重要的预后信息。
