The ganglioside GD2 as a circulating tumor biomarker for neuroblastoma

Background G(D2) is a ganglioside that is ubiquitously expressed in the plasma membrane of neuroblastoma and is shed into the circulation. Procedure G(D2) was measured with a high-pressure liquid chromatography/tandem mass spectrometry assay in serum or plasma from 40 children without cancer (controls) and in biobanked samples from 128 (73 high-risk) children with neuroblastic tumors at diagnosis, 56 children with relapsed neuroblastoma, 14 children with high-risk neuroblastoma after treatment, and 8 to 12 children each with 10 other common childhood cancers at diagnosis. Results The C-18 (18 carbon fatty acid) lipoform was the predominant circulating form of G(D2) in controls and in patients with neuroblastoma. The median concentration of G(D2) in children with high-risk neuroblastoma at diagnosis was 167 nM (range, 16.1-1060 nM), which was 30-fold higher than the median concentration (5.6 nM) in controls. G(D2) was not elevated in serum from children with the differentiated neuroblastic tumors, ganglioneuroma (n = 10) and ganglioneuroblastoma-intermixed subtype (n = 12), and in children with 10 other childhood cancers. G(D2) concentrations were significantly higher in serum from children with MYCN-amplified tumors (P = 0.0088), high-risk tumors (P < 0.00001), International Neuroblastoma Staging System (INSS) stage 4 tumors (P < 0.00001), and in children who died (P = 0.034). Conclusions Circulating G(D2) appears to be a specific and sensitive tumor biomarker for high-risk/high-stage neuroblastoma and may prove to be clinically useful as a diagnostic or prognostic circulating tumor biomarker. G(D2) will be measured prospectively and longitudinally in children enrolled on a high-risk neuroblastoma treatment trial to assess its ability to measure response to treatment and predict survival.