ArticleCell biology and toxicology2023
Prognostic significance of NT5E/CD73 in neuroblastoma and its function in CSC stemness maintenance.
Article in Cell biology and toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 8 citations in OpenAlex.
- Purinergic system in cancer stem cells.Purinergic signalling · 2025Review
- Proteasome Inhibition Reprograms Chromatin Landscape in Breast Cancer.Cancer research communications · 2024Article
- Mesenchymal stem cell-based TRAIL delivery inhibits the metastatic state of clinical therapy-resistant progressive neuroblastoma.World journal of pediatrics : WJP · 2024Article
- ATP and Adenosine Metabolism in Cancer: Exploitation for Therapeutic Gain.Pharmacological reviews · 2022Review
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Authors and funding
7 authors at 2 institutions in 1 country.
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Abstract
Cluster of differentiation 73 (CD73), a cell surface enzyme that catalyzes adenosine monophosphate (AMP) breakdown to adenosine, is differentially expressed in cancers and has prognostic significance. We investigated its expression profile in neuroblastoma (NB), its association with NB clinical outcomes, and its influence in the regulation of cancer stem cells' (CSCs) stemness maintenance. RNA-Seq data mining (22 independent study cohorts, total n = 3836) indicated that high CD73 can predict good NB prognosis. CD73 expression (immunohistochemistry) gauged in an NB patient cohort (n = 87) showed a positive correlation with longer overall survival (OS, P = 0.0239) and relapse-free survival (RFS, P = 0.0242). Similarly, high CD73 correlated with longer OS and RFS in advanced disease stages, MYCN non-amplified (MYCN-na), and Stage-4-MYCN-na subsets. Despite no definite association in children < 2 years old (2Y), high CD73 correlated with longer OS (P = 0.0294) and RFS (P = 0.0315) in children > 2Y. Consistently, high CD73 was associated with better OS in MYCN-na, high-risk, and stage-4 subsets of children > 2Y. Multivariate analysis identified CD73 as an independent (P = 0.001) prognostic factor for NB. Silencing CD73 in patient-derived (stage 4, progressive disease) CHLA-171 and CHLA-172 cells revealed cell-line-independent activation of 58 CSC stemness maintenance molecules (QPCR profiling). Overexpressing CD73 in CHLA-20 and CHLA-90 cells with low CD73 and silencing in CHLA-171 and CHLA-172 cells with high CD73 showed that CD73 regulates epithelial to mesenchymal transition (E-Cadherin, N-Cadherin, Vimentin), stemness maintenance (Sox2, Nanog, Oct3/4), self-renewal capacity (Notch), and differentiation inhibition (leukemia inhibitory factor, LIF) proteins (confocal-immunofluorescence). These results demonstrate that high CD73 can predict good prognosis in NB, and further suggest that CD73 regulates stemness maintenance in cells that defy clinical therapy.
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