Neuropeptide May Serve as Biomarker for Neuroblastoma Patients

By LabMedica International staff writers
Posted on 26 Oct 2016
A study has found the common nerve protein Neuropeptide Y (NPY) to be elevated in the blood of those with an aggressive form of neuroblastoma, suggesting that NPY could serve as biomarker in a prognostic and/or treatment monitoring test, and as a new target for developing a more effective therapeutic drug for this early childhood cancer.

There are various types of neuroblastoma, ranging from spontaneously regressing to untreatable fatal tumors. 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,” said study leader Joanna Kitlinska, PhD, associate professor, Georgetown University Medical Center (Washington, DC, USA).

Image: A microscopic view of a typical neuroblastoma with rosette formation (Photo courtesy of Dr. Maria Tsokos, National Cancer Institute).

Because of their neuronal origin, neuroblastomas synthesize and release neuropeptide Y (NPY), a small protein normally secreted from mature nerves. Previously, Prof. Kitlinska and colleagues showed that NPY, acting via its Y2 and Y5 receptors (Y2R and Y5R), is crucial for maintaining neuroblastoma growth and protecting the tumors from chemotherapy.

“To confirm the clinical relevance of our earlier work and assess NPY and its receptors as potential prognostic factors, we performed clinical study on tissue samples and serum from 87 neuroblastoma patients,” said Prof. Kitlinska, “We have found that NPY is released from aggressive neuroblastoma tumors 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.” High NPY release is a strong marker of metastatic disease, and 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.

“These results support the previously described crucial role for NPY in neuroblastoma biology, and suggest its contribution to the disease dissemination and resistance to therapy. Thus, our study validates the NPY system as a potential therapeutic target and potential prognostic marker for neuroblastoma,” she said, “In contrast to complex genetic analyses currently utilized to assess risk of the disease, the measurement of NPY levels in blood can be converted to a readily available analytical test. Using such easily accessible clinical material may also allow for minimally invasive longitudinal monitoring of the disease progression.”

If confirmed by further prospective studies, this finding may have a significant impact on the clinical management of children with neuroblastoma.

The study, by Susana Galli S et al, was published online October 12, 2016, in the American Journal of Pathology.

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