Shed tumor gangliosides and progression of human neuroblastoma.
Shedding of membrane gangliosides is characteristic of human and experimental tumors. Because some shed tumor gangliosides have potent tumor-enhancing properties, significant ganglioside shedding could influence tumor progression. We examined this possibility in a human tumor, neuroblastoma. Ganglioside shedding, measured as circulating tumor-derived GD2 ganglioside, and the outcome of 74 patients with advanced stage (III and IV) disease were studied. Progression-free survival (PFS) was inversely related to circulating GD2 levels at the time of diagnosis (P = .018). By Kaplan-Meier analysis, the quartile of patients having the highest circulating GD2 levels (greater than or equal to 568 pmol/mL) had a strikingly different outcome from the quartile of patients with the lowest (less than or equal to 103 pmol/mL) GD2 levels (P = .013): median PFS was shorter (9 v 28 months), and the long-term survival rate lower (2-year PFS of 24% v 70%). We conclude that more rapid disease progression and lower survival rate are associated with high circulating GD2 levels at diagnosis and speculate that shed neuroblastoma tumor gangliosides play a role in accelerating tumor progression.
Valentino
L
L
Department of Pediatrics, UCLA School of Medicine 90024-1752.
Moss
T
T
Olson
E
E
Wang
H J
HJ
Elashoff
R
R
Ladisch
S
S
D014408:Biomarkers, Tumor / Q000097:blood* / Q000302:isolation & purification; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005500:Follow-Up Studies; D005732:Gangliosides / Q000097:blood* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000097:blood / Q000473:pathology*; D011379:Prognosis
D014408:Biomarkers, Tumor; D005732:Gangliosides