The ganglioside, GD2, as a circulating tumor biomarker for neuroblastoma
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Oct 15, 2019 version files 30.61 KB
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GD2Biomarker.xlsx
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Abstract
Background: GD2 is a ganglioside that is ubiquitously expressed in the plasma membrane of neuroblastoma
and is shed into the circulation.
Procedure: GD2 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 C18 (18 carbon fatty acid) lipoform was the predominant circulating form of
GD2 in controls and in patients with neuroblastoma. The median concentration of GD2 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. GD2 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.
GD2 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 GD2 appears to be a specific and sensitive tumor biomarker for highrisk/
high-stage neuroblastoma and may prove to be clinically useful as a diagnostic or prognostic
circulating tumor biomarker. GD2 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.
This was a retrospective analysis. Serum samples were obtained from several biorepositories. The C18 and C20 lipoforms of GD2 were measured in the serum samples using a validated HPLC/MS/MS assay