• Pengxian Tao, Lei Gao, Haiyuan Li, Bofang Wang, Xuemei Li, Ying Zhang, and Hao Chen.
• The Department of Tumor Surgery, Lanzhou University Second Hospital.
• Medicine (Baltimore). 2020 Dec 24; 99 (52): e23841.

BackgroundPrevious studies have showed that the high expression of urokinase plasminogen activator (uPA) in pathology and serology is closely related to the progression of hepatocellular carcinoma (HCC). However, there are no systematic reviews for these evidence, and the association between uPA and HCC is still not completely understood. Therefore, we will undertake a systematic review of the literature to summarize previous evidence regarding this topic, in order to clarify the prognostic significance of uPA in HCC.Methods And AnalysisStudies comparing the HCC patients with high and low expression of uPA on the clinicopathological features and the prognosis are eligible for this review. Outcomes include all endpoints about survival and clinicopathological features. Prospective or retrospective primary studies which published in English will be included. Four databases of Medline, EMBASE, Web of Science, and the Cochrane Library will be systematically searched from their inception to Mar 2021 to retrieve relevant studies. Reference lists of included studies will be manually reviewed and grey literatures will be identified by Google Scholar. Two reviewers will independently screen the records and extract the information and data of the included studies. The Newcastle-Ottawa Scale will be used to assess the quality of included studies. Hazard ratio and 95% confidence interval will be pooled to assess the association between uPA expression and the prognosis. Pooled odds ratio and 95% confidence interval will be used for other outcomes. Heterogeneity will be assessed using the Cochrane Q test and I2 statistic, and a subgroup analysis will be performed if necessary. Grades of Recommendation, Assessment, Development and Evaluation method will be applied to assess the certainty of evidence.Ethics And DisseminationThis protocol required information extracted from previously published articles. So, there is no ethical problem in this study. We plan to publish our findings in peer-reviewed journals and relevant conference proceedings.Systematic Review RegistrationThis study has been registered with the International Prospective Register of Systematic Reviews database (no.CRD42020150340).Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.

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