MPC-8 Serum anti-zinc finger FYVE domain-containing protein 21 (ZFYVE21) autoantibody as a novel biomarker for oligodendroglioma IDH-mutant and 1p/19q co-deletion

Background: Glioma is one of the most challenging diseases to cure, and it would be beneficial to discover new serum biomarkers for early diagnosis. Moreover, zinc finger FYVE domain-containing protein 21 (ZFYVE21) was a regulator of tumor invasion and migration. In this study, we examined the levels of serum anti-ZFYVE21 antibodies in patients with glioma. Methods: This is a multicenter observational prospective study to discover a novel serum autologous antibody marker. We analyzed 286 pre-surgically collected sera of CNS tumors and compared them to healthy donors(HD). Bacterially expressed glutathione-S-transferase-fused ZFYVE21 protein was purified, and its antibody levels were measured by amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). Results: The anti-ZFYVE21 antibody levels were significantly elevated in patients with gliomas (P<0.001) than those in HD, instead of patients with other CNS tumors. Among gliomas, the highest sensitivity was observed for oligodendroglioma containing IDH mutation and 1p/19q co-deletion to HD (sensitivity: 72.00%, specificity: 67.71%, AUC: 0.7565, P<0.0001), while there is no significance in astrocytoma containing only IDH mutation. In comparing 1p/19q co-deleted oligodendroglioma with IDH-mutated astrocytoma, the sensitivity and specificity were 50% and 100%, respectively. Conclusion: Serum anti-ZFYVE21 antibodies might be a novel diagnostic marker distinguishing 1p/19q co-deleted oligodendroglioma from IDH-mutant astrocytoma.