HNK-1 Antibody-Based ELISA for Soluble PTPRZ: A Practical Cerebrospinal Fluid Biomarker for Glioma

Reliable fluid biomarkers for glioma remain elusive, complicating diagnosis and differentiation from primary central nervous system lymphoma (PCNSL). We evaluated soluble protein tyrosine phosphatase receptor type Z (sPTPRZ) in cerebrospinal fluid (CSF) using an anti-HNK-1 antibody-based ELISA. CSF sPTPRZ levels were significantly elevated in glioma patients compared with controls (AUC = 0.910) and moderately distinguished gliomas from PCNSL (AUC = 0.805). Immunohistochemistry and qPCR confirmed lack of PTPRZ expression in PCNSL, while epitope mapping localized the HNK-1 modification site to exon 12 of the long isoform. RNA-seq of the C-CAT database revealed PTPRZ-MET fusions in 2% of gliomas, all lacking the HNK-1 epitope, consistent with low CSF sPTPRZ in a subset of tumors. These findings establish CSF sPTPRZ detection with anti-HNK-1 antibody as a minimally invasive and robust biomarker for glioma, supporting improved diagnostic accuracy and aiding clinical decision-making in neuro-oncology.