Investigative needle core biopsies support multimodal deep-data generation in glioblastoma Journal Article
| Authors: | Yu, K. K. H.; Basu, S.; Baquer, G.; Ahn, R.; Gantchev, J.; Jindal, S.; Regan, M. S.; Abou-Mrad, Z.; Prabhu, M. C.; Williams, M. J.; D’Souza, A. D.; Malinowski, S. W.; Hopland, K.; Elhanati, Y.; Stopka, S. A.; Stortchevoi, A.; Couturier, C.; He, Z.; Sun, J.; Chen, Y.; Espejo, A. B.; Chow, K. H.; Yerrum, S.; Kao, P. L.; Kerrigan, B. P.; Norberg, L.; Nielsen, D.; The GBM TeamLab; Puduvalli, V. K.; Huse, J.; Beroukhim, R.; Kim, B. Y. S.; Goswami, S.; Boire, A.; Frisken, S.; Cima, M. J.; Holdhoff, M.; Lucas, C. H. G.; Bettegowda, C.; Levine, S. S.; Bale, T. A.; Brennan, C.; Reardon, D. A.; Lang, F. F.; Chiocca, E. A.; Ligon, K. L.; White, F. M.; Sharma, P.; Tabar, V.; Agar, N. Y. R. |
| Article Title: | Investigative needle core biopsies support multimodal deep-data generation in glioblastoma |
| 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. © The Author(s) 2025. |
| Keywords: | epidermal growth factor; mitogen activated protein kinase; platelet derived growth factor; clinical article; controlled study; human tissue; treatment response; unclassified drug; genetics; clinical trial; brain tumor; brain neoplasms; t lymphocyte; mouse; animal; metabolism; animals; mice; stat3 protein; cohort analysis; tumor xenograft; drug screening; pathology; xenograft model antitumor assays; protein tyrosine kinase; proteomics; transcriptomics; rna; t lymphocyte receptor; immune response; brain; adenosine; janus kinase; tumor recurrence; cancer testis antigen; glioblastoma; diagnosis; needle biopsy; data analysis; ligand; genomics; craniotomy; protein tyrosine phosphatase; adenosine triphosphate; cell interaction; transcriptome; disease exacerbation; stereotactic procedure; phosphoprotein; immunocompetent cell; stereotactic biopsy; peroperative care; genetic heterogeneity; chlordane; major histocompatibility antigen class 1; cd163 antigen; cell surface receptor; adenosine phosphate; programmed death 1 ligand 1; stat protein; neuronavigation; linoleic acid; metabolomics; single cell analysis; single-cell analysis; data set; stereotaxic techniques; osteopontin; nicotinamide adenine dinucleotide phosphate; terpenoid; procedures; small nuclear rna; peptidomics; chemokine receptor cx3cr1; polyunsaturated fatty acid; immune checkpoint inhibitor; phosphoproteomics; biopsy, large-core needle; large core needle biopsy; cancer; humans; human; female; article; data integration; proteogenomics; immunopeptidomics; single cell rna seq; multiomics; allograft inflammatory factor 1; cd226 antigen; 6 o methylguanine; epsilon opiate receptor; p2ry12 protein; sirpalpha protein; small cytoplasmic rna; sorl1 protein; multimodal deep data generation |
| Journal Title: | Nature Communications |
| Volume: | 16 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2025-04-28 |
| Start Page: | 3957 |
| Language: | English |
| DOI: | 10.1038/s41467-025-58452-8 |
| PUBMED: | 40295505 |
| PROVIDER: | scopus |
| PMCID: | PMC12037860 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Viviane Tabar -- Source: Scopus |
