Identification of plasma Complement C3 as a potential biomarker for neuroblastoma using a quantitative proteomic approach

Abstract

This study has utilised a unique murine model which develops neuroblastoma tumours that are biologically indistinguishable from human neuroblastoma. This animal model has effectively allowed the identification of plasma proteins which may serve as potential biomarkers of neuroblastoma. Furthermore, the label-free ion count quantitation technique which was used displays significant benefits as it is less labour intensive, feasible and accurate. We have been able to successfully validate this approach by confirming the differential abundance of two different plasma proteins. In addition, we have been able to confirm that the candidate biomarker Complement C3, is more abundant in the plasma of human neuroblastoma patient plasma samples when compared to healthy counterparts. Overall we have demonstrated that this approach can be potentially useful in the identification of biomarker candidates, and that further validation of the candidates may lead to the discovery of novel, clinically useful diagnostic tools in the detection of sub-clinical neuroblastoma.

GD2‐targeted immunotherapy and potential value of circulating microRNAs in neuroblastoma

“…Several studies showed that NB is a heterogeneous and complex disease and a lot of factors such as stage of disease, age, and genetic alterations involved in progression of this malignancy (Brodeur & Bagatell, ; Fathullahzadeh, Mirzaei, Honardoost, Sahebkar, & Salehi, ; Louis & Shohet, ; Maris, ; H. Mirzaei, Khataminfar, et al, ; Schleiermacher, Janoueix‐Lerosey, & Delattre, ; Simonian, Mosallayi, & Mirzaei, ). Beside genetic heterogeneity and aberrant epigenetic regulation, abnormal expression of small non‐coding RNAs (miRNAs) has revealed indispensable role in NB establishment and resistance to current standard treatments (Chen & Stallings, ; Kim et al, ; McClure & Shirataki, ). Different expression of miRNAs between MYC amplified and non‐amplified human neuroblastoma tumors corroborated the role of miRNAs in neurblastoma pathogenesis (Beckers et al, ; Buechner & Einvik, ; Chen & Stallings, ; Schulte et al, ).…”

“…In one study, identification of plasma Complement C3 as a potential biomarker for NB using a quantitative proteomic approach. They have demonstrated the suitability of the TH‐MYCN +/+ mouse model of NB for identification of novel disease biomarkers in humans, and have identified Complement C3 as a candidate plasma biomarker for measuring disease state in NB patients (Kim et al, ). In other study, Sandoval et al (), the utilizing of proteomics approaches for investigating other proteins profiles as new candidate serum biomarkers in an established animal model of advance stage human NB.…”

“…Mirzaei, Khataminfar, et al, 2016;Schleiermacher, Janoueix-Lerosey, & Delattre, 2014;Simonian, Mosallayi, & Mirzaei, 2016). Beside genetic heterogeneity and aberrant epigenetic regulation, abnormal expression of small noncoding RNAs (miRNAs) has revealed indispensable role in NB establishment and resistance to current standard treatments (Chen & Stallings, 2007;Kim et al, 2014;McClure & Shirataki, 1989).…”

An engineered high affinity Fbs1 carbohydrate binding protein for selective capture of N-glycans and N-glycopeptides

“…7c). Figure 7d shows the N-glycosylation micro-heterogeneity analysis for a single potential disease biomarker, human Complement C343. In this case, Fbs1 GYR enrichment clearly allows identification of more glycan types and spectra at each glycosite relative to the pre-enrichment and lectin enrichment samples.…”

Proteomics of dedifferentiation of SK-N-BE2 neuroblastoma cells

“…Proteomics-based studies of neuroblastoma has identified complement C3 protein as being highly expressed in the plasma of human neuroblastoma samples [10]. Genomic abberations were reported as important markers in treatment of neuroblastoma [11][12][13][14].…”