Cerebrospinal fluid sPTPRZ detected with HNK-1 antibody as a practical biomarker for glioma diagnosis

Abstract Background A major challenge in managing gliomas is the lack of reliable and clinically applicable biomarkers. Imaging alone is often insufficient to distinguish gliomas from primary central nervous system lymphoma (PCNSL), necessitating invasive biopsy. Soluble protein tyrosine phosphatase receptor type Z (sPTPRZ) in cerebrospinal fluid (CSF) has recently emerged as a promising candidate. We evaluated the diagnostic utility of CSF sPTPRZ in differentiating gliomas from PCNSL. Methods We developed an anti-HNK-1 antibody-based ELISA for CSF sPTPRZ and analyzed 51 glioma, 15 PCNSL, and 20 control patients. Complementary assays included western blotting, immunohistochemistry, qPCR. sPTPRZ immunopurified from glioma CSF was used to determine HNK-1 epitope sites. RNA-seq data from the C-CAT database were used to identify PTPRZ gene fusions. Results CSF sPTPRZ levels were significantly elevated in glioma patients compared with both controls and PCNSL, demonstrating robust discrimination between these entities (AUC = 0.910 vs controls; AUC = 0.805 vs PCNSL; P = .0010). PTPRZ expression was absent in PCNSL, consistent with low CSF sPTPRZ. Mass spectrometry localized the HNK-1 epitope to exon 12 of PTPRZ-long, absent in PTPRZ-MET fusion variants (2% of gliomas). These insights may explain low sPTPRZ levels in a subset of gliomas. Conclusion CSF sPTPRZ detection with anti-HNK-1 antibody is a minimally invasive biomarker for glioma. It significantly improves diagnostic discrimination from PCNSL, and provides a molecular rationale for biomarker-negative glioma subsets with PTPRZ-MET fusions.