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.
Highlights
An area other than the SVZ, is termed SVZ-negative (SVZn)
This can be achieved with the help of autoantibody response towards certain aberrant self-proteins termed as tumour associated autoantigens (TAAs) using protein microarray based platforms
We have identified potential candidate proteins, which are able to distinguish the healthy controls from various grades of glioma, and the sub-types observed in case of the aggressive GBM, which provides the necessary groundwork for minimal invasive diagnostics of this disease
Summary
An area other than the SVZ, is termed SVZ-negative (SVZn). The prognosis of SVZn patients has been reported to be better than SVZp subjects, making the proximity of GBMs to the SVZ, a potential predictor of survival[6]. The extent of invasiveness and risks involved in brain biopsies required to establish disease condition necessitates the need for novel serum based biomarkers to incorporate minimal invasive diagnosis[9]. This can be achieved with the help of autoantibody response towards certain aberrant self-proteins termed as tumour associated autoantigens (TAAs) using protein microarray based platforms. We have identified potential candidate proteins, which are able to distinguish the healthy controls from various grades of glioma, and the sub-types observed in case of the aggressive GBM, which provides the necessary groundwork for minimal invasive diagnostics of this disease
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