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The urokinase plasminogen activation system in gastroesophageal cancer: A
systematic review and meta-analysis
#MMPMID28416743
Brungs D
; Chen J
; Aghmesheh M
; Vine KL
; Becker TM
; Carolan MG
; Ranson M
Oncotarget
2017[Apr]; 8
(14
): 23099-23109
PMID28416743
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BACKGROUND: 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. RESULTS: 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. MATERIALS AND METHODS: 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). CONCLUSIONS: 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.
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