Novel immunogenic antigens increase classification accuracy in meningioma to 93.84%

Abstract

There is growing evidence that simultaneous analysis of multiple autoantibody reactions can be utilized for diagnosis of neoplasms. Using a set of 57 meningioma-associated antigens, we recently separated meningioma patients from individuals without known disease with an accuracy of 90.3%. Here, we ask whether a largely increased set of immunogenic antigens can further improve this discrimination. We used an array with 1,827 human recombinant clones and measured reactivity of serum autoantibodies against the clones by a novel automated image analysis procedure. We were able to separate meningioma sera from sera of healthy controls with a specificity of 95.62%, a sensitivity of 91.83% and an accuracy of 93.84%. Of the analyzed clones, 23 in-frame clones were highly informative for the classification of meningioma vs. normal sera as shown by their AUC values. These results demonstrate that the accuracy of a serum-based diagnostic can be readily and considerably improved by screening extended sets of proteins.

Myasthenia Gravis: Analysis of Serum Autoantibody Reactivities to 1827 Potential Human Autoantigens by Protein Macroarrays

“…This finding is in marked contrast to results from previous autoantibody screens carried out with the same autoantigen macroarray in patients with lung cancer, glioma, and meningioma [27], [28], [29]. Indeed, autoantibody signatures discriminated sera from patients with lung cancer from healthy control sera with a specificity, sensitivity, and accuracy of ≥97% each [27] and allowed to separate glioma sera from healthy control sera with a specificity of 90.5%, a sensitivity of 85.9%, and an accuracy of 88.5% [28].…”

“…Indeed, previous work performed in patients with various cancers as well as autoimmune diseases suggests that autoantibody profiles may have the potential to serve as disease biomarkers and to provide clues for disease pathogenesis [20], [21], [22], [23], [24], [25], [26]. Accordingly, a customized protein macroarray comprising 1827 potential human autoantigens recently developed in our laboratory permitted to adequately discriminate sera of patients with different cancers from sera of healthy controls [27], [28], [29]. However, this customized macroarray has not yet been evaluated in antibody-mediated autoimmune diseases.…”

Multicenter study identified molecular blood‐born protein signatures for Wilms Tumor

“…Such autoantibody signatures are described for a variety of cancers including prostate cancer, lung cancer and ovarian cancer 14–17. Recently, we reported highly specific and sensitive autoantibody signatures for glioma, meningioma and lung cancer 18–20…”

Secretion and Immunogenicity of the Meningioma-Associated Antigen TXNDC16

“…Each classified peptide value was multiplied with its corresponding duplicate on the same peptide array, therefore resulting in four final classifying groups (4, strong seropositive; 2, moderate seropositive; 1, weak seropositive; and 0, seronegative). For the serum classification, linear support vector machines with 20 repetitions of standard 10-fold crossvalidation were used as described previously (5). Unprocessed raw data can be downloaded from National Center for Biotechnology Information Gene Expression Omnibus (www.ncbi.nlm.nih.gov/geo/index.cgi), accession number GSE58949.…”

“…They occur with an average annual incidence of 7 in 100,000 and are generally benign (1,2). We previously showed that meningiomas trigger a complex humoral immune response, suitable for a highly accurate minimally invasive detection by serological methods (3)(4)(5). Serological screening of recombinantly expressed clones revealed several meningioma-associated Ags reacting with patients' sera.…”