Prognostic Role of Circulating Soluble uPAR in Various Cancers: a Systematic Review and Meta-Analysis.

Abstract Soluble uPAR (suPAR) is a soluble fraction of uPAR which is an important cell surface receptor. Recent evidence suggests that circulating suPAR levels are elevated in multiple malignancies and associated with prognosis of patients, although the results are not consistent. This study aimed to analyze the effect of suPAR on the prognosis in various carcinomas through a systematic review and meta-analysis. Eligible studies were searched in PubMed and EMBASE. Data were extracted from studies investigating the relationship between circulating suPAR and survival in patients with cancers. A meta-analysis of the hazard ratio (HR) was then performed to evaluate the prognostic role of suPAR in various carcinomas. Pooled HRs of suPAR for overall survival (OS) were calculated to measure the effect of circulating suPAR level on prognosis. After the literature search and systematic review, 12 articles regarding suPAR (I - III + II - III) including 2878 patients were included in a meta-analysis, which indicated a significantly poor OS in patients with high expression levels of circulating suPAR in subgroups of colorectal cancer (CRC), ovarian cancer, breast cancer, and prostate cancer (total HR 1.63, 95% CI 1.46 - 1.81) , and this effect is most obvious in patients with CRC (HR 1.67, 95% CI 1.47 - 1.89). No evidence of heterogeneity and publication bias was present. Our results suggested that suPAR is a promising biomarker in the prediction of prognosis in patients with cancers. However, further studies are warranted to validate its clinical application and biological implication with tumor development.