Identification of plasma biomarker candidates in glioblastoma using an antibody-array-based proteomic approach

Abstract

BackgroundGlioblastoma multiforme (GBM) is a brain tumour with a very high patient mortality rate, with a median survival of 47 weeks. This might be improved by the identification of novel diagnostic, prognostic and predictive therapy-response biomarkers, preferentially through the monitoring of the patient blood. The aim of this study was to define the impact of GBM in terms of alterations of the plasma protein levels in these patients.Materials and methods.We used a commercially available antibody array that includes 656 antibodies to analyse blood plasma samples from 17 healthy volunteers in comparison with 17 blood plasma samples from patients with GBM.ResultsWe identified 11 plasma proteins that are statistically most strongly associated with the presence of GBM. These proteins belong to three functional signalling pathways: T-cell signalling and immune responses; cell adhesion and migration; and cell-cycle control and apoptosis. Thus, we can consider this identified set of proteins as potential diagnostic biomarker candidates for GBM. In addition, a set of 16 plasma proteins were significantly associated with the overall survival of these patients with GBM. Guanine nucleotide binding protein alpha (GNAO1) was associated with both GBM presence and survival of patients with GBM.ConclusionsAntibody array analysis represents a useful tool for the screening of plasma samples for potential cancer biomarker candidates in small-scale exploratory experiments; however, clinical validation of these candidates requires their further evaluation in a larger study on an independent cohort of patients.

A preliminary investigation of circulating extracellular vesicles and biomarker discovery associated with treatment response in head and neck squamous cell carcinoma

“…Utilization of peripheral blood for the discovery of tumor biomarkers is a very practical approach because it is minimally invasive, inexpensive, highly reproducible, and it could mitigate the intra-temporal heterogeneity-sampling problem [30]. Zupancic et al (2014) [31] analyzed non-depleted plasma samples of healthy volunteers in comparison to glioblastoma multiform (GBM) patients using antibody arrays and identified 11 plasma proteins as biomarker candidates for the diagnosis and prognosis of patients with GBM. Although plasma and serum are reliable sources for cancer biomarker discovery, its usage has several limitations as previously discussed [20].…”

GNAO1 encephalopathy

“… 18 GNAO1 has also been implicated in the etiology of brain tumors, such as ependymoma and glioblastoma multiforme. 19 , 20 …”

OSgbm: An Online Consensus Survival Analysis Web Server for Glioblastoma

“…To determine the performance of this online tool, 53 previously published GBM prognostic factors collected as the procedure shown in Figure S1 and then they were evaluated in OSgbm (Table 2, Figure 1) (Sano et al, 1999;Hung and Howng, 2003;Heimberger et al, 2005;Aaberg-Jessen et al, 2009;Shirai et al, 2009;Pu et al, 2011;Cui et al, 2013;De Tayrac et al, 2013;Lee et al, 2013;Rosati et al, 2013;Wang et al, 2013;Wu et al, 2013;Bai et al, 2014;Han et al, 2014;Meng et al, 2014;Olmez et al, 2014;Zupancic et al, 2014;Maris et al, 2015;Moutal et al, 2015;Yan et al, 2015;Zhao et al, 2015;Chaurasia et al, 2016;Nduom et al, 2016;Steponaitis et al, 2016;Steponaitis et al, 2016;Zhang et al, 2016a;Zhang et al, 2016b;Deng et al, 2017;Dong et al, 2017;Ge et al, 2017;Han et al, 2017;Haynes et al, 2017;Huang et al, 2017;Li et al, 2017;Luo and Zhuang, 2017;Ma et al, 2017;Roy et al, 2017;Wu et al, 2017;Zhang et al, 2017;…”