Abstract
Symptomatic glioma is usually not curable due to its invasive nature into surrounding normal brain. Establishment of serum biomarkers for gliomas would be beneficial both for early diagnosis and adequate post-operative monitoring. We searched for novel glioma antigens by serological identification of antigens utilizing recombinant cDNA expression cloning (SEREX), and found three independent proteins including filamin C (FLNC), SH3-domain GRB2-like 1 (SH3GL1), and pyruvate kinase M2 (PKM2) as candidate proteins. We analyzed with ELISA 131 glioma patients' sera along with 77 sera from healthy volunteers, 19 sera from patients with meningioma, and 24 patients with cerebral infarction. All the levels of serum autoantibodies to these proteins were significantly higher in low-grade gliomas than in high-grade gliomas, the healthy volunteers and the patients with other benign disease. In contrast, these proteins were expressed in glioma tissues and its level got higher as tumor grade advanced. The discrepancy was caused by the immunosuppressive microenvironments due to mesenchymal cell infiltration, which was verified by immunohistochemistry and ELISA for the mesenchymal cell-specific proteins. The rat glioma models using C6 and 9L also confirmed the increase of autoantibody levels for the SEREX-identified proteins in the early stage and the suppression in the late stage. These proteins were involved in the oncogenic process of gliomas and effectively elicit autologous antibody responses in the glioma patients without immunosuppression. The immunological reaction to some glioma antigens would contribute to the establishment of a novel diagnostic and therapeutic target for gliomas.
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