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

Naruse, Y.; Fujii, M.; Nagai, K.; Hiruta, R.; Sakagami, T.; Kobayashi, T.; Takahashi, K.; Iijima, J.; Suzuki, H.; Oka, Y.; Hashimoto, Y.; Hattori, K.; Kanai, K.; Koriyama, S.; Saito, T.; Muragaki, Y.; Kawamata, T.; Sasayama, T.; Yasuda, J.; Uzuki, M.; Kawaguchi, Y.; kawata, K.; Yamaguchi, Y.; Go, S.; Arakawa, H.; Kaji, H.; Kitazume, S.

2025-08-21 oncology
10.1101/2025.08.19.25332842 medRxiv
Show abstract

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.

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