尿激酶-纤溶酶原激活系统（uPA）在接受根治性膀胱切除术（RC）治疗的膀胱癌患者中的预后价值。

The prognostic value of the urokinase-plasminogen activator system (uPA) in bladder cancer patients treated with radical cystectomy (RC).

机构信息

Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Medical University of Hamburg, Hamburg, Germany.

Department of Urology, Medical University of Vienna, Vienna, Austria.

出版信息

Urol Oncol. 2020 May;38(5):423-432. doi: 10.1016/j.urolonc.2020.02.002. Epub 2020 Mar 21.

DOI:10.1016/j.urolonc.2020.02.002

PMID:32209281

Abstract

PURPOSE

Urokinase-plasminogen activator (uPA), its receptor (uPAR), and the plasmin-activator inhibitor type 1 (PAI-1) have been associated with oncologic outcomes in various malignancies and could help identify bladder cancer (BC) patients treated with radical cystectomy (RC) who are likely to benefit from intensification of therapy to prevent disease progression. Our aim was to assess the value of uPA, uPAR, and PAI-1 for prognosticating survival outcomes of patients treated with RC for BC.

MATERIALS AND METHODS

Tumor specimens from 272 consecutive patients treated with RC for advanced BC were assessed with immunohistochemical staining for uPA, uPAR, and PAI-1. Overexpression was assessed by pathological image analysis. Kaplan-Meier estimates and multivariable Cox-regression were used to analyze survival. Harrell's C-index was used to assess for clinical impact of the uPA system.

RESULTS

uPA, uPAR, and PAI-1 were overexpressed in 48.2%, 51.1%, and 52.2% of patients, respectively. uPA overexpression was associated with lymphovascular invasion (P = 0.034) and nodal status (P = 0.013); PAI-1 overexpression was associated with primary muscle-invasive BC (P = 0.015) and lymphovascular invasion (P = 0.024). uPA, uPAR, and the number of overexpressed markers were all 3 significantly associated with shorter overall recurrence-free-, distant recurrence-free-, and cancer-specific survival. In multivariable analyses, uPA overexpression remained associated with shorter recurrence-free survival (hazard ratio [HR] = 1.79; P = 0.036) in the entire cohort, in patients without lymph node metastasis (HR = 1.98; P = 0.018) and those with nonorgan-confined disease (HR = 1.98; P = 0.022). uPAR overexpression was associated with shorter recurrence-free survival in patients without lymph node metastasis (HR = 2.01; P = 0.021) and those with organ-confined disease (HR = 4.11; P = 0.037).

CONCLUSION

Members of the uPA system are associated with features of biologically aggressive BC and oncologic outcomes. However, their value beyond currently available information remains limited.

摘要

目的

尿激酶型纤溶酶原激活物（uPA）、其受体（uPAR）和纤溶酶原激活物抑制剂 1（PAI-1）与多种恶性肿瘤的肿瘤学结果相关，并可帮助识别接受根治性膀胱切除术（RC）治疗的膀胱癌（BC）患者，这些患者可能受益于强化治疗以预防疾病进展。我们的目的是评估 uPA、uPAR 和 PAI-1 对接受 RC 治疗的 BC 患者生存结果的预后价值。

材料和方法

对 272 例接受 RC 治疗的晚期 BC 患者的肿瘤标本进行免疫组织化学染色，以评估 uPA、uPAR 和 PAI-1 的表达。通过病理图像分析评估过表达。Kaplan-Meier 估计和多变量 Cox 回归用于分析生存情况。Harrell's C 指数用于评估 uPA 系统的临床影响。

结果

uPA、uPAR 和 PAI-1 在 48.2%、51.1%和 52.2%的患者中过表达。uPA 过表达与脉管侵犯（P=0.034）和淋巴结状态（P=0.013）相关；PAI-1 过表达与原发性肌层浸润性 BC（P=0.015）和脉管侵犯（P=0.024）相关。uPA、uPAR 和过表达标志物的数量均与总无复发生存期、无远处复发生存期和癌症特异性生存期较短显著相关。多变量分析显示，uPA 过表达在整个队列中仍与较短的无复发生存期相关（风险比[HR]为 1.79；P=0.036），在无淋巴结转移的患者（HR 为 1.98；P=0.018）和非器官受限疾病的患者（HR 为 1.98；P=0.022）中。uPAR 过表达与无淋巴结转移的患者（HR 为 2.01；P=0.021）和器官受限疾病的患者（HR 为 4.11；P=0.037）的无复发生存期较短相关。