Human studies show specific nerve cell protein is elevated by an aggressive form of neuroblastoma.

A protein produced by nerve cells appears to be elevated in the blood of those with an aggressive form of neuroblastoma. The findings, presented at the American Association for Cancer Research 2015 Annual Meeting, could potentially lead to a prognostic test for the disease or be used to monitor its progress.

The team from Georgetown University explain that neuroblastoma is a pediatric cancer with varying types, ranging from spontaneously regressing to untreatable fatal tumours. Consequently, treatment strategies vary significantly between patients, encompassing different approaches including observation alone or intensive chemo- and radiotherapy.  Given the severe late effects of anti-cancer treatment administered to infants and children, proper disease stratification is of utmost importance for neuroblastoma patients, state the team.

Because of their neuronal origin, neuroblastomas synthesize and release neuropeptide Y (NPY), a small protein normally secreted from mature nerves. In previous research the researchers have shown that NPY, acting via its Y2 and Y5 receptors (Y2R and Y5R), is crucial for maintaining neuroblastoma growth and protecting the tumours from chemotherapy.

To confirm the clinical relevance of their earlier work and assess NPY and its receptors as potential prognostic factors, the team performed a clinical study on tissue samples and serum from 87 neuroblastoma patients.  The data findings showed that NPY is released from aggressive neuroblastoma tumours into the blood, which results in its elevated serum concentrations. These high systemic levels of NPY are associated with several adverse prognostic factors for neuroblastoma and worse survival of neuroblastoma patients.

The team state that high NPY release is a strong marker of metastatic disease, while the Y5R is present preferentially in invasive neuroblastoma cells. Also, patients with elevated NPY at diagnosis were more likely to have a disease relapse in the future.  The group go on to add that these results support a crucial role for NPY in neuroblastoma biology, particularly in its dissemination and resistance to therapy, and validate the NPY system as a potential therapeutic target and potential prognostic marker for neuroblastoma.

In contrast to complex genetic analyses currently utilized to assess risk of the disease, the team state that the measurement of NPY levels in blood can be converted to a readily available analytical test. Using such easily accessible clinical material will allow for minimally invasive longitudinal monitoring of the disease progression.

The team now plan to confirm the findings of the current study with further prospective studies, concluding that the results may have a significant impact on the clinical management of patients with neuroblastoma.

Source:  Georgetown University Medical Center

Differentiating neuroblastoma cells stained for microtubules (purple), actin (green).  Credit:  Torsten Wittmann, PhD.   UCSF Biomedical Sciences.

Differentiating neuroblastoma cells stained for microtubules (purple), actin (green). Credit: Torsten Wittmann, PhD. UCSF Biomedical Sciences.

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