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.

The authors have declared no competing interest.

Funding This work was supported by AMED (grant numbers JP22cm0106484 and JP 24ama221440), the Mizutani Foundation for Glycoscience (to S.K.), and a grant from the International Joint Research Project of the Institute of Medical Science, the University of Tokyo, and by the joint research program of the J-GlycoNet cooperative network (25C012), which is accredited by the Minister of Education, Culture, Sports, Science and Technology, MEXT, Japan as a Joint Usage/Research Center.

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Ethics This study was approved by the ethics committee of Fukushima Medical University (approval numbers 2020-287 and 29378), which is guided by local policy, national laws, and the World Medical Association Declaration of Helsinki.

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The LC-MS/MS data generated in this study have been deposited in jPOST database under accession number [JPST003723/PXD062244]. Other datasets generated or analyzed during the current study are available from the corresponding author S. Kitazume upon reasonable request.