Investigative needle core biopsies support multimodal deep-data generation in glioblastoma
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.
Authors
- Ryuhjin Ahn (ORCID: https://orcid.org/0000-0001-9788-4401)
- Keith Lloyd Ligon (ORCID: https://orcid.org/0000-0002-7733-600X)
- Yuval Elhanati (ORCID: https://orcid.org/0000-0002-4354-8864)
- Jennifer Gantchev (ORCID: https://orcid.org/0000-0001-5236-0671)
- Smitha Yerrum
- Lisa Norberg (ORCID: https://orcid.org/0009-0007-5741-8773)
- Pei-Lun Kao
- Kenny Kwok Hei Yu (ORCID: https://orcid.org/0000-0002-2394-4990)
- Kelsey Hopland
- Alexsandra Espejo (ORCID: https://orcid.org/0000-0002-8841-7219)
- Alicia D. D’Souza (ORCID: https://orcid.org/0000-0001-7635-7573)
- Seth Malinowski (ORCID: https://orcid.org/0000-0001-6468-3451)
- Gerard Baquer (ORCID: https://orcid.org/0000-0002-4433-4972)
- Sonali Jindal (ORCID: https://orcid.org/0000-0002-3911-6815)
- Sylwia A. Stopka (ORCID: https://orcid.org/0000-0003-3761-6899)
- Michael S. Regan (ORCID: https://orcid.org/0000-0001-5252-2829)
- Sreyashi Basu (ORCID: https://orcid.org/0000-0002-5028-3833)
- Alexei Stortchevoi (ORCID: https://orcid.org/0000-0001-9916-4344)
- Brittany C. Parker Kerrigan (ORCID: https://orcid.org/0009-0005-9268-0342)
- Michael C. Prabhu
- Marc Williams (ORCID: https://orcid.org/0000-0001-5524-4174)
- Zaki Abou-Mrad (ORCID: https://orcid.org/0000-0001-6387-8396)
- Douglas Nielsen
- Yulong Chen (ORCID: https://orcid.org/0009-0003-1436-9300)
- Zhong He (ORCID: https://orcid.org/0000-0002-7369-9989)
- Jingjing Sun (ORCID: https://orcid.org/0000-0002-3087-8258)
- Charles Couturier (ORCID: https://orcid.org/0000-0001-8015-7160)
- Kin Hoe Chow
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Memorial Sloan Kettering Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Harvard University (US)
- Johns Hopkins University (US)
- Johns Hopkins Medicine (US)
- Harvard–MIT Division of Health Sciences and Technology (US)
- Center for Neuro-Oncology (US)
- Dana-Farber Cancer Institute (US)
- Dana-Farber/Harvard Cancer Center (US)
- Sidney Kimmel Comprehensive Cancer Center (US)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-28
- DOI
- https://doi.org/10.1038/s41467-025-58452-8
- Citations
- 9
- Primary Topic
- Cell Image Analysis Techniques
- Type
- article
- Field-Weighted Citation Impact
- 14.71
Funders
- Memorial Sloan-Kettering Cancer Center
- Massachusetts Life Sciences Center
- Break Through Cancer
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- National Institutes of Health
- University of Texas MD Anderson Cancer Center
- Ludwig Center at Harvard
- Canadian Institutes of Health Research
- National Cancer Institute