Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, PR China.
Oncol Rep. 2013 Feb;29(2):637-45. doi: 10.3892/or.2012.2148. Epub 2012 Nov 20.
The urokinase plasminogen activator system, which consists of urokinase plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1) and urokinase plasminogen activator receptor (uPAR), plays an important role in tumor invasion and metastasis, and it may be a potential diagnostic biomarker and therapeutic target in cancer. It has been found that the expression of uPA and PAI-1 in ovarian cancer is related to clinical pathologies, while their effects on the biological behavior of tumor cells and their clinical significance are still unknown. In this study, 100 tissue samples (60 samples from malignant tumors, 20 from benign tumors and 20 from controls) and 147 blood samples (49 samples each from patients with malignant tumors, benign tumors and control group, respectively) were analyzed. The positive expression levels of uPA and PAI-1 in the malignant tumor samples and their serum concentrations in the malignant group were all significantly higher than these levels in the benign tumors and controls. In addition, the levels in patients with poorly differentiated and stage III-IV cancers, cancers with metastases as well as residual tumors >2 cm after surgery, were all obviously increased, consistent with their concentrations in serum. The Cox model analysis showed that expression of uPA at the transcription level had significant associations with prognosis. In addition, uPA greatly enhanced the abilities of cell invasion, migration and adhesion through its overexpression in SKOV3 cells. Collectively, our results showed that uPA and PAI-1 play important roles in ovarian cancer development; therefore, their expression in tissues and their concentrations in serum would greatly assist the diagnosis and prediction of the prognosis in ovarian cancer.
尿激酶型纤溶酶原激活物系统(urokinase plasminogen activator system,uPA)由尿激酶型纤溶酶原激活物(urokinase plasminogen activator,uPA)、纤溶酶原激活物抑制剂 1(plasminogen activator inhibitor type-1,PAI-1)和尿激酶型纤溶酶原激活物受体(urokinase plasminogen activator receptor,uPAR)组成,在肿瘤侵袭和转移中发挥重要作用,它可能是癌症诊断的潜在生物标志物和治疗靶点。已经发现卵巢癌中 uPA 和 PAI-1 的表达与临床病理有关,但其对肿瘤细胞生物学行为的影响及其临床意义尚不清楚。本研究分析了 100 个组织样本(恶性肿瘤 60 例,良性肿瘤 20 例,对照组 20 例)和 147 个血清样本(恶性肿瘤组各 49 例,良性肿瘤组和对照组各 49 例)。恶性肿瘤组织中 uPA 和 PAI-1 的阳性表达水平及其血清浓度均明显高于良性肿瘤和对照组。此外,在分化不良和 III-IV 期癌症、有转移以及术后残留肿瘤>2cm 的患者中,水平明显升高,与血清浓度一致。Cox 模型分析显示,uPA 在转录水平的表达与预后显著相关。此外,uPA 在 SKOV3 细胞中的过表达显著增强了细胞侵袭、迁移和黏附能力。综上所述,我们的研究结果表明 uPA 和 PAI-1 在卵巢癌的发展中起重要作用;因此,其在组织中的表达和血清中的浓度将极大地有助于卵巢癌的诊断和预后预测。