Abstract 1954: Metabolic serum signatures as potential prognostic biomarkers for neuroblastoma patients
Authors: Richa Jain, Kirandeep Gill, Leon Qingliang Li, Amrita K. Cheema, Joanna B. Kitlinska
Journal: Cancer Research (2017)

Abstract Neuroblastoma (NB) is a pediatric malignancy with phenotypes varying from spontaneously regressing to metastatic tumors. Thus, disease stratification and the subsequent treatment decision is of utmost importance for NB patients. The methods, which are currently available for prognosis, require complex genetic analyses and access to the tumor tissue. Thus, there is a need for new prognostic and predictive markers that reflect the NB biology and rely on simple tests and easily accessible material. Serum metabolite profiles reflect a combination of factors released by the tumors and the general metabolic state of the patients. Thus, identifying the differences in metabolites between patients with various tumor phenotypes and responses to treatment may lead to discovery of biologically relevant prognostic biomarkers. The goal of our study was to determine blood-based metabolic signatures characteristic for patients with low and high-risk NB and identify potential biomarkers of high-risk disease. Plasma samples from NB patients at different stages of the disease were obtained from the Children’s Oncology Group. Initially, 50 samples were analyzed by Ultra Performance Liquid Chromatography (UPLC) in conjunction with electrospray-quadrupole-time of flight mass spectrometry (ESI-Q-TOF). A set of 26 independent plasma samples was then used for validation study. Statistically significant differences in metabolic profiles were observed between serum from patients with low and high risk disease, various stages of the disease (stage 1-2 vs stage 3 and/or stage 4), as well as undifferentiated vs. differentiating tumors. For all comparisons, the metabolic signatures consisting of metabolites significantly different between the groups exhibited high test sensitivity and specificity (the area under the ROC curves 0.92-1). Metabolites that were dysregulated in high risk NBs included those involved in energy and choline metabolism, as well as amino acid and lipid biosynthesis. Of particular interest was a significant increase in serum levels of oxoglutaric acid observed in patients with high-risk disease (p&amp;lt;0.01) and metastatic tumors (p&amp;lt;0.001). As oxoglutaric acid is a key metabolite of the tricarboxylic acid (TCA) cycle that is involved in regulation of the balance between glutamine and glucose metabolism, as well as lipid synthesis and hypoxia response, these data warrant further investigations into the biological role of these pathways in biology of high risk NB. In summary, using a metabolomics approach we were able to delineate blood based biomarkers that could potentially be used for patient stratification following large scale validation studies. Citation Format: Richa Jain, Kirandeep Gill, Leon Qingliang Li, Amrita K. Cheema, Joanna B. Kitlinska. Metabolic serum signatures as potential prognostic biomarkers for neuroblastoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1954. doi:10.1158/1538-7445.AM2017-1954