Longitudinal profiling of cerebrospinal fluid N-glycome dynamics in glioblastoma patients treated with apatinib

Abstract

Glioblastoma (GBM) remains a therapeutically intractable central nervous system malignancy with limited treatment options. Apatinib, a selective vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, shows emerging potential in recurrent or refractory glioblastoma, yet its impact on the cerebrospinal fluid (CSF) glycome remains unexplored. In this pioneering longitudinal study, we characterize the N-glycome dynamics in paired CSF specimens from GBM patients pre- and post-apatinib treatment using hydrophilic interaction-based ultra performance liquid chromatography (HILIC-UPLC)-fluorescence mass spectrometry-based glycan profiling. Our results highlight potential alterations in specific glycoforms, particularly an increase in GalNAcβ1–4GlcNAc (LacdiNAc or LDN), core fucosylation(a modification catalyzed by α1,6-fucosyltransferase (Fut8), which transfers L-fucose from GDP-fucose to the innermost GlcNAc residue), and bisecting glycans(a β1,4-linked GlcNAc attached to the core β-mannose residue), a decrease in sialylation and biantennary glycans among treatment responders. These shifts correlate with attenuated immunosuppressive signatures, suggesting enhanced immunomodulation that may contribute to apatinib’s therapeutic efficacy. This work uncovers the remodeling of the CSF glycome driven by apatinib, providing a novel molecular lens for understanding its anti-angiogenic/immune-modulating mechanisms and proposing CSF N-glycans as dynamic biomarkers for treatment efficacy in GBM.