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The urokinase plasminogen activation system in gastroesophageal cancer: A systematic review and meta-analysis.

ABSTRACT: 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.

SUBMITTER: Brungs D

PROVIDER: S-EPMC5410288 | biostudies-other | 2017 Apr

REPOSITORIES: biostudies-other

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The urokinase plasminogen activation system in gastroesophageal cancer: A systematic review and meta-analysis.

Brungs Daniel D Chen Julia J Aghmesheh Morteza M Vine Kara L KL Becker Therese M TM Carolan Martin G MG Ranson Marie M

Oncotarget 20170401 14

<h4>Background</h4>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.<h4>Results</h4>We identified 22 studies encompassing 1966 patients which fulfilled the inclusion criteria. uPA, uPAR, or PAI-1 expression is significantly associated with high risk clinicopa ...[more]

PMID: 28416743

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Project description:OBJECTIVES:Soluble urokinase plasminogen activated receptor (suPAR) is a biomarker that may predict the occurrence of focal segmental glomerulosclerosis (FSGS); however, there is still controversy about whether suPAR can predict FSGS. In this study, we performed a systematic evaluation and meta-analysis to prove whether suPAR can predict FSGS, and to detect a threshold concentration of suPAR that can be used to diagnose FSGS. In addition, a threshold concentration of suPAR for the diagnosis of FSGS was proposed. DESIGN:Systematic review and meta-analysis. DATA SOURCES:We systematically searched PubMed, Embase, Cochrane Library, Web of Science and China Biology Medicine databases for studies published from the inception dates to 1 December 2018. ELIGIBILITY CRITERIA: (1) Data involving the suPAR level were from blood samples; (2) FSGS was diagnosed by biopsy; and (3) randomised controlled trials, cohort studies, case-control studies and cross-sectional studies. DATA EXTRACTION AND SYNTHESIS:Initially, a total of 364 studies were searched, among which 29 studies were finally included. In addition, seven studies described the cut-off value of suPAR, which ranged from 2992.6 to 5500?pg/mL. RESULTS:The results showed that the suPAR levels in the primary FSGS group were significantly higher when compared with that in the normal control group (p<0.001; standard mean difference (SMD): 2.56; 95% CI 1.85 to 3.28), and significant differences were observed in the secondary FSGS and in the normal control group (p<0.001; SMD: 1.68; 95%?CI 1.37 to 1.98). A suPAR concentration of 3000?pg/mL may be the best threshold for the diagnosis of primary FSGS (sensitivity=0.72; specificity=0.88; area under the curve=0.85). CONCLUSION:Our results suggested that suPAR might be a potential biomarker for predicting primary and secondary FSGS. In addition, our data showed that a suPAR concentration of 3000?pg/mL might be used as a threshold for the diagnosis of FSGS. TRIAL REGISTRATION NUMBER:CRD42019120948.

Project description:BACKGROUND:Gastroesophageal reflux disease (GERD), which leads to acid reflux into the esophagus, is a common gastrointestinal disorder. Several studies have shown the prevalence of GERD in Iranian population, but their evidence is contradictory. Therefore, the present study was conducted to investigate the epidemiology of GERD in Iran. METHODS:The entire steps of this systematic review and meta-analysis were based on the MOOSE protocol, and the results were reported accordance with the PRISMA guideline. This review is registered on PROSPERO (registration number: CRD42020142861). To find potentially relevant published articles, comprehensive search was done on international online databases Scopus, Science Direct, EMBASE, PubMed/Medline, CINAHL, EBSCO, Cochrane Library, Web of Science, Iranian online databases and the Google Scholar search engine in June 2019. Cochran test and I2 index were used to assess the heterogeneity of the studies. Data were analyzed using Comprehensive Meta-Analysis software ver. 2. The significance level of the test was considered to be P?<? 0.05. RESULTS:The daily, weekly, monthly, and overall prevalence of GERD symptoms in Iranian population was 5.64% (95%CI [confidence interval]: 3.77-8.35%; N?=?66,398), 12.50% (95%CI: 9.63-16.08%; N?=?110,388), 18.62% (95%CI: 12.90-26.12%; N?=?70,749) and 43.07% (95%CI: 35.00-51.53%; N?=?73,189), respectively. The daily, weekly, monthly, and overall prevalence of heartburn in Iranian population was 2.46% (95%CI: 0.93-6.39%; N?=?18,774), 9.52% (95%CI: 6.16-14.41%; N?=?54,125), 8.19% (95%CI: 2.42-24.30%; N?=?19,363) and 23.20% (95%CI: 13.56-36.79%; N?=?26,543), respectively. The daily, weekly, monthly, and overall prevalence of regurgitation in Iranian population was 4.00% (95%CI: 1.88-8.32%; N?=?18,774), 9.79% (95%CI: 5.99-15.60%; N?=?41,140), 13.76% (95%CI: 6.18-44.31%; N?=?19,363) and 36.53% (95%CI: 19.30-58.08%; N?=?21,174), respectively. The sensitivity analysis for prevalence of all types GERD, heartburn and regurgitation symptoms by removing a study showed that the overall estimate is still robust. CONCLUSION:The present meta-analysis provides comprehensive and useful information on the epidemiology of GERD in Iran for policy-makers and health care providers. This study showed a high prevalence of GERD in Iran. Therefore, effective measures on GERD-related factors such as lifestyle can be among the health policies of Iran.

Dataset Information

The urokinase plasminogen activation system in gastroesophageal cancer: A systematic review and meta-analysis.

Publications

The urokinase plasminogen activation system in gastroesophageal cancer: A systematic review and meta-analysis.

Similar Datasets

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