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.

Activation of IL-8 and its participation in cancer in schizophrenia patients: new evidence for the autoimmune hypothesis of schizophrenia

“…Although autoimmunity in cancer is yet to be thoroughly investigated, increasing numbers of studies suggest that aggravated autoimmune responses play a crucial role in manifestation of cancer. Autoantibody targets such as IGHG4, CRYM, EFCAB2, STAT6, HDAC7A and CCNB1 were significantly deregulated across all grades of meningioma 37. In cancer, both active and passive immunotherapies have been tested with promising results, which is similar to the immunotherapies applied to several autoimmune diseases 38–41.…”

Anti-Cancer Auto-Antibodies: Roles, Applications and Open Issues

“…Another study evaluated the proteome signature of meningiomas using human proteome arrays. The study results showed that several proteins overexpressed in grade I and grade II meningiomas are known targets of auto-antibodies, such as IGHG4, CRYM, EFCAB2, STAT6, HDAC7A, and CCNB1 [ 28 ]. In a different study, circulating anti-pituitary (APA) and anti-hypothalamus (AHA) antibodies were evaluated in children with CNS tumors.…”

AAgMarker 1.0: a resource of serological autoantigen biomarkers for clinical diagnosis and prognosis of various human diseases

“…Many reasons, including different methods of data process and biomarker identification, could contribute to this discrepancy. Researchers may use different signal calling methods, such as Foreground-Background ( 17 ); they may use one or more different parameters, such as signalling rate of 15% in diseases and 0% in controls ( 18 ), sensitivity at 95% specificity ( 14 ); they may use different cutoff values, namely P values of <0.01 versus <0.05 ( 5 ). In addition, some studies only provided an incomplete list of biomarkers, or focused on biomarkers showing significantly high reactivity in patient groups compared to the healthy controls ( 13 ).…”