Abstract
CD73 is a glycosylphosphatidylinositol (GPI) anchored cell surface protein that is encoded by NT5E gene, plays multiple roles in tumor processes. Previous studies have presented a potential value of CD73 served as a detectable biomarker for prognosis of several solid tumors, but the results were more controversially. A comprehensive meta-analysis was conducted to precisely evaluate the prognostic role of CD73 in solid tumors. The included studies were searched in PubMed, Web of Science and EBSCO from Jan 1990 to Jan 2016. Pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for overall survival (OS), disease free survival (DFS) were carried out using a fixed or random effects model. Totally, 13 studies about 12,533 patients were included. CD73-high expression was correlating with poor OS (pooled HR = 1.28, 95% CI = 1.19–1.37). In addition, CD73 expression had borderline association with worse DFS (pooled HR = 1.28, 95% CI = 1.01–1.62). Egger’s tests indicated that there was no evidence of significant publication bias. CD73 is an efficient prognostic biomarker in solid tumors, and over-expression of CD73 is associated with inverse OS or DFS. But this predictive value and target therapy for clinical practice yet needs advanced research.
Highlights
CD73, known as ecto-5’-nucleotidase (NT5E), is a glycosylphosphatidylinositol linked cell surface enzyme found in normal tissues
1039 potential studies were yielded utilizing the electronic databases search, of which 13 articles met the inclusion criteria (Figure 2). Those relevant relevant articles were screened for eligibility by duplication and language, and 760 records were excluded. 256 articles were excluded through title and abstract screening
CD73-adenosinergic pathway has been involved in the pathophysiology of substantial solid tumors
Summary
CD73, known as ecto-5’-nucleotidase (NT5E), is a glycosylphosphatidylinositol linked cell surface enzyme found in normal tissues. Recent studies implied that CD73 was over-expressed on various kinds of solid malignant tumors (i.e., breast cancer [2], colorectal cancer [3], prostate cancer [4], ovarian cancer [5], and gallbladder cancer [6]). CD73 plays a pivotal role for tumor cells proliferation, angiogenesis and apoptosis, via modulating extrinsic signaling, like EGFR/Akt, VEGF/Akt pathway and impairing antitumor immunity [11, 12]. Extracellular ADO can exert effect on tumor immune microenvironment through multiple pathways [1, 13]: 1) Limiting cytotoxic activity of effective immune cells: ADO significantly reduces CD8+. 3) Inducing anomalous differentiation and weakening the function of antigen presenting cells: ADO bonding with A2B receptor can alter dendritic cells phenotype, decrease the level of tumor antigen presentation, and increase vascular endothelial growth factor (VEGF) production [20, 21]. For purpose of more precisely evaluate the prognostic value of CD73adenosinergic pathway in solid tumor, a systematic review and meta-analysis was conducted according to previous published studies
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