GD2 ganglioside, a known specific marker for neuroblastoma (NB), exists in different lipoforms, including C18 and C20, which are distinguished by the length of their fatty acid chains. C18 and C20 GD2 lipoforms can be simultaneously measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We evaluated the diagnostic and prognostic performance of circulating GD2 levels in children with NB.
Thirty microliters of peripheral blood (PB) plasma samples from 83 children with NB at diagnosis and 83 age-matched healthy controls were analyzed by LC-MS/MS. From stage M patients, 29 additional PB plasma samples were collected after induction therapy, 7 before and after immunotherapy, and 6 at relapse. For 22 stage M patients, bone marrow (BM) plasma samples were also collected at diagnosis.
C18 and C20 GD2 concentrations were significantly higher in children with NB than in controls. Receiver operating characteristic (ROC) analysis showed a cut-point of 44.1 and 0.47 nM for C18 and C20, respectively, able to discriminate with high specificity and sensitivity in patients with NB from controls. Circulating C18 and C20 levels in PB strongly correlated with those in BM. At diagnosis, C18 and C20 GD2 concentrations were significantly higher in stage M, deceased patients, and in those bearing tumors with MYCN amplification. ROC analysis identified prognostic cut points for the whole population, whereas only C20 concentrations above the cut points were significantly associated with a worse event-free survival of patients with stage M disease or with MYCN-amplified tumors. C18 and C20 plasma concentrations strongly decreased during treatment but increased at relapse.
Measurement of circulating GD2 seems to have prognostic power in the subsets of patients with stage M disease and with MYCN-amplified tumors, and be able to early detect relapse, thus its ability to monitor disease should be prospectively evaluated in future studies.
© The Author(s) 2025. Published by Oxford University Press.

While better management of loco-regional prostate cancer (PC) has greatly improved survival, advanced PC remains a major cause of cancer deaths. Identification of novel targetable pathways that contribute to tumor progression in PC could open new therapeutic options. The di-ganglioside GD2 is a target of FDA-approved antibody therapies in neuroblastoma, but the role of GD2 in PC is unexplored. Here, we show that GD2 is expressed in a small subpopulation of PC cells in a subset of patients and a higher proportion of metastatic tumors. Variable levels of cell surface GD2 expression were seen on many PC cell lines, and the expression was highly upregulated by experimental induction of lineage progression or enzalutamide resistance in CRPC cell models. GD2high cell fraction was enriched upon growth of PC cells as tumorspheres and GD2high fraction was enriched in tumorsphere-forming ability. CRISPR-Cas9 knockout (KO) of the rate-limiting GD2 biosynthetic enzyme GD3 Synthase (GD3S) in GD2high CRPC cell models markedly impaired the in vitro oncogenic traits and growth as bone-implanted xenograft tumors and reduced the cancer stem cell and epithelial-mesenchymal transition marker expression. Our results support the potential role of GD3S and its product GD2 in promoting PC tumorigenesis by maintaining cancer stem cells and suggest the potential for GD2 targeting in advanced PC.
© 2024. The Author(s).