Neuroblastoma is the third-most-common solid
tumor of childhood. To date, no reliable blood marker for
neuroblastoma has been established. The
growth factor midkine is highly expressed in human
carcinomas and its knockdown leads to
tumor growth suppression in animal models. The present study evaluated the plasma
midkine level in human
neuroblastoma patients. Plasma samples were obtained from patients found through mass screening, as well as from sporadic
neuroblastoma patients. The total number of cases examined was 756. Among them, prognostic information was available for 175 sporadic cases and 287 mass-screening cases.
Midkine levels were significantly higher in
neuroblastoma patients, including both mass-screening cases and sporadic cases, than in non-
tumor controls (P < 0.0001). The
midkine level was significantly correlated with the statuses of MYCN amplification, TRKA expression, ploidy, stage and age (P < 0.0001, < 0.0001, = 0.004, < 0.0001 and < 0.0001, respectively), which are known prognostic factors for
neuroblastoma. There was a striking correlation between high plasma
midkine level and poor prognosis (P < 0.0001). Within sporadic cases, the
midkine level was also strikingly higher than in non-
tumor controls (P < 0.0001), and correlated with the statuses of MYCN amplification and stage (P = 0.0005 and = 0.003, respectively). There was a significant correlation between high plasma
midkine level and poor prognosis (P = 0.04). Taken together, the present data indicate that plasma
midkine level is a prognostic factor for human
neuroblastoma.