Serum Protein N-Glycosylation Signatures of Neuroblastoma

Abstract

BackgroundNeuroblastoma is the most common extracranial childhood solid tumor which accounts for 10% of the malignancies and 15% of the cancer fatalities in children. N-glycosylation is one of the most frequent post-translation protein modification playing a vital role in numerous cancers. N-glycosylation changes in neuroblastoma patient serum have not been studied in existing reports. The comprehensive analyses of serum N-glycomics in neuroblastoma can provide useful information of potential disease biomarkers and new insights of the pathophysiology in neuroblastoma.MethodsThe total serum protein N-glycosylation was analyzed in 33 neuroblastoma patients and 40 age- and sex-matched non-malignant controls. N-glycans were enzymatically released, derivatized to discriminate linkage-specific sialic acid, purified by HILIC-SPE, and identified by MALDI-TOF-MS. Peak areas were acquired by the software of MALDI-MS sample acquisition, processed and analyzed by the software of Progenesis MALDI.ResultsThree glyco-subclasses and six individual N-glycans were significantly changed in neuroblastoma patients compared with controls. The decreased levels of high mannose N-glycans, hybrid N-glycans, and increased levels of α2,3-sialylated N-glycans, multi-branched sialylated N-glycans were observed in neuroblastoma patients. what is more, a glycan panel combining those six individual N-glycans showed a strong discrimination performance, with an AUC value of 0.8477.ConclusionsThis study provides new insights into N-glycosylation characteristics in neuroblastoma patient serum. The analyses of total serum protein N-glycosylation could discriminate neuroblastoma patients from non-malignant controls. The alterations of the N-glycomics may play a suggestive role for neuroblastoma diagnosis and advance our understanding of the pathophysiology in neuroblastoma.

Sialic Acid-Siglec Axis in Human Immune Regulation, Involvement in Autoimmunity and Cancer and Potential Therapeutic Treatments

“…The presence of a certain degree of variability observed in the expression of Siglec ligands in cancers of different tissue-specific origin is implicated in the different immune escape strategies and thus influences the possible therapeutic approaches relying on Siglecs or their ligands [ 105 ]. The serum protein N-glycosylation signatures observed recently in neuroblastoma patients could potentially represent disease biomarkers [ 106 ]. In addition, aberrant glycosylation might constitute a possible marker to identify those patients resistant to standard chemotherapy as observed recently by Zahradnikova [ 107 ] who revealed an association between N-glycome modifications and resistance to platinum-based chemotherapy in ovarian cancer.…”