Autoantibody Profiling of Glioma Serum Samples to Identify Biomarkers Using Human Proteome Arrays

Abstract

The heterogeneity and poor prognosis associated with gliomas, makes biomarker identification imperative. Here, we report autoantibody signatures across various grades of glioma serum samples and sub-categories of glioblastoma multiforme using Human Proteome chips containing ~17000 full-length human proteins. The deduced sets of classifier proteins helped to distinguish Grade II, III and IV samples from the healthy subjects with 88, 89 and 94% sensitivity and 87, 100 and 73% specificity, respectively. Proteins namely, SNX1, EYA1, PQBP1 and IGHG1 showed dysregulation across various grades. Sub-classes of GBM, based on its proximity to the sub-ventricular zone, have been reported to have different prognostic outcomes. To this end, we identified dysregulation of NEDD9, a protein involved in cell migration, with probable prognostic potential. Another subcategory of patients where the IDH1 gene is mutated, are known to have better prognosis as compared to patients carrying the wild type gene. On a comparison of these two cohorts, we found STUB1 and YWHAH proteins dysregulated in Grade II glioma patients. In addition to common pathways associated with tumourigenesis, we found enrichment of immunoregulatory and cytoskeletal remodelling pathways, emphasizing the need to explore biochemical alterations arising due to autoimmune responses in glioma.

Prognostic value of preoperative von Willebrand factor plasma levels in patients with Glioblastoma

“…In the last years, new proteomic approaches allow the identification of circulating plasma proteins which reflect disease biology, and have been considered a useful option to discover potential biomarkers for brain tumors 8. Among the most relevant candidates, angiogenic factors, have been found to play a pivotal role in GBM onset and progression 9.…”

An overview of innovations and industrial solutions in Protein Microarray Technology

“…Interestingly, Heng Zhu, who was one of the lead co‐workers alongside Michael Snyder, had independently developed these functional arrays to device yeast, herpes virus, Escherichia coli , rice blast fungus, and human “proteome‐on‐a‐chip.” One of the popular chips developed by this group is the Human Protein Array chips, referred to as HuProt, containing as many as 17 000 full‐length GST‐tagged human recombinant proteins. These have been popularly used by various groups for biomarker and protein interaction screening . These arrays now manufactured by CDI Laboratories feature more than 19 000 recombinant human proteins, and are few of the highly dense protein arrays available (Table a).…”

“…In addition to that, the short shelf‐life, lack of universal binding partners, and amplification modalities for proteins add to the complexity of developing protein arrays . However, timely innovations in this domain have helped in overcoming many of these obstacles and proved to be useful in numerous interactions‐based studies . A powerful and high‐throughput platform such as protein array relies extensively on technological innovations at every stage right from chip printing, assembly, detection, and data acquisition .…”

Protein microarray applications: Autoantibody detection and posttranslational modification

“…(A) Schematic diagram represents the generalized process of sample detection by a protein microarray platform. (B) HuProt array of ∼17 000 full‐length proteins used to analyze and identify biomarkers from Glioma patient/control serum samples . (C) An in‐house printed antibody array of ≈3600 antibodies incubated plasma or serum samples to carry out a HT screen for native autoantigen–Aab complexes .…”