The urokinase plasminogen activation system in gastroesophageal cancer: A systematic review and meta-analysis.
The urokinase plasminogen activation system in gastroesophageal cancer: A systematic review and meta-analysis.
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DOI：
10.18632/oncotarget.15485
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发表时间：
2017-04-04
期刊：
影响因子：
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通讯作者：
Ranson M
中科院分区：
文献类型：
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作者：
Brungs D;Chen J;Aghmesheh M;Vine KL;Becker TM;Carolan MG;Ranson M
尿激酶纤溶酶原激活（uPA）系统是肿瘤侵袭和转移的关键途径。尽管有充分的证据表明uPA系统表达是某些实体瘤中的临床相关生物标志物，但其在胃食管癌中的作用尚不确定。我们确定了22项研究，包括1966例符合纳入标准的患者。uPA、uPAR或派-1表达与高危临床病理特征显著相关。高uPA表达与较短的RFS（HR 1.90 95% 1.16-3.11，p = 0.01）和OS（HR 2.21 95% CI 1.74-2.80，p < 0.0001）相关。高uPAR表达与较差OS相关（HR 2.21 95%CI 1.82-2.69，p < 0.0001）。高派-1表达与较短的RFS（HR 1.96 96%CI 1.07-3.58，p = 0.03）和OS（HR 1.84 95%CI 1.28-2.64，p < 0.0001）相关。派-2表达与OS之间无显著相关性（HR 0.97 95%CI 0.48-1.94，p < 0.92），尽管数据有限。我们对uPA、尿激酶型纤溶酶原激活物受体（uPAR）、纤溶酶原激活物抑制剂-1（派-1/SerpinE 1）和纤溶酶原激活物抑制剂-2（派-2/SerpinB 2）在原发性食管癌、胃食管交界处癌和胃腺癌中的表达进行了系统评价。我们对临床病理学相关性、总生存期（OS）和无复发生存期（RFS）进行了荟萃分析。我们的结论是uPA系统是一个临床相关的生物标志物在原发性胃食管癌，与高表达的uPA，uPAR和派-1与高风险的疾病和预后较差。这也突出了uPA系统作为改善治疗策略的治疗靶点的潜在效用。
The urokinase plasminogen activation (uPA) system is a crucial pathway for tumour invasion and establishment of metastasis. Although there is good evidence that uPA system expression is a clinically relevant biomarker in some solid tumours, its role in gastroesophageal cancer is uncertain. We identified 22 studies encompassing 1966 patients which fulfilled the inclusion criteria. uPA, uPAR, or PAI-1 expression is significantly associated with high risk clinicopathological features. High uPA expression is associated with a shorter RFS (HR 1.90 95% 1.16–3.11, p = 0.01) and OS (HR 2.21 95% CI 1.74–2.80, p < 0.0001). High uPAR expression is associated with poorer OS (HR 2.21 95%CI 1.82–2.69, p < 0.0001). High PAI-1 expression is associated with shorter RFS (HR 1.96 96% CI 1.07–3.58, p = 0.03) and OS (HR 1.84 95%CI 1.28–2.64, p < 0.0001). There was no significant association between PAI-2 expression and OS (HR 0.97 95%CI 0.48–1.94, p < 0.92) although data was limited. We undertook a systematic review evaluating expression of uPA, urokinase plasminogen activator receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1/SerpinE1) and plasminogen activator inhibitor-2 (PAI-2/SerpinB2) on primary oesophageal, gastro-oesophageal junction, and gastric adenocarcinomas. We performed a meta-analysis of clinicopathological associations, overall survival (OS) and recurrence free survival (RFS). We conclude that the uPA system is a clinically relevant biomarker in primary gastroesophageal cancer, with higher expression of uPA, uPAR and PAI-1 associated with higher risk disease and poorer prognosis. This also highlights the potential utility of the uPA system as a therapeutic target for improved treatment strategies.