Faculty, Staff and Student Publications

Publication Date

4-28-2025

Journal

Nature Communications

DOI

10.1038/s41467-025-58452-8

PMID

40295505

PMCID

PMC12037860

PubMedCentral® Posted Date

4-28-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Glioblastoma (GBM) is an aggressive primary brain cancer with few effective therapies. Stereotactic needle biopsies are routinely used for diagnosis; however, the feasibility and utility of investigative biopsies to monitor treatment response remains ill-defined. Here, we demonstrate the depth of data generation possible from routine stereotactic needle core biopsies and perform highly resolved multi-omics analyses, including single-cell RNA sequencing, spatial transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics on standard biopsy tissue obtained intra-operatively. We also examine biopsies taken from different locations and provide a framework for measuring spatial and genomic heterogeneity. Finally, we investigate the utility of stereotactic biopsies as a method for generating patient-derived xenograft (PDX) models. Multimodal dataset integration highlights spatially mapped immune cell-associated metabolic pathways and validates inferred cell-cell ligand-receptor interactions. In conclusion, investigative biopsies provide data-rich insight into disease processes and may be useful in evaluating treatment responses.

Keywords

Glioblastoma, Humans, Animals, Brain Neoplasms, Mice, Biopsy, Large-Core Needle, Proteomics, Metabolomics, Xenograft Model Antitumor Assays, Single-Cell Analysis, Female, Stereotaxic Techniques, Transcriptome

Published Open-Access

yes

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