Evaluation of autoantibody signatures in meningioma patients using human proteome arrays

Abstract

Meningiomas are one of the most common tumors of the Central nervous system (CNS). This study aims to identify the autoantibody biomarkers in meningiomas using high-density human proteome arrays (~17,000 full-length recombinant human proteins). Screening of sera from 15 unaffected healthy individuals, 10 individuals with meningioma grade I and 5 with meningioma grade II was performed. This comprehensive proteomics based investigation revealed the dysregulation of 489 and 104 proteins in grades I and II of meningioma, respectively, along with the enrichment of several signalling pathways, which might play a crucial role in the manifestation of the disease. Autoantibody targets like IGHG4, CRYM, EFCAB2, STAT6, HDAC7A and CCNB1 were significantly dysregulated across both the grades. Further, we compared this to the tissue proteome and gene expression profile from GEO database. Previously reported upregulated proteins from meningioma tissue-based proteomics obtained from high-resolution mass spectrometry demonstrated an aggravated autoimmune response, emphasizing the clinical relevance of these targets. Some of these targets like SELENBP1 were tested for their presence in tumor tissue using immunoblotting. In the light of highly invasive diagnostic modalities employed to diagnose CNS tumors like meningioma, these autoantibody markers offer a minimally invasive diagnostic platform which could be pursued further for clinical translation.