Dataset Information

Investigative needle core biopsies support multimodal deep-data generation in glioblastoma

ABSTRACT: Glioblastoma (GBM) is a primary brain cancer with an abysmal prognosis with few effective therapies. The ability to investigate the tumor microenvironment before and during treatment would greatly enhance both our understanding of disease response and progression, as well as the delivery and impact of therapeutics. Stereotactic biopsies are a routine surgical procedure performed primarily for diagnostic histopathologic purposes. The adaptation of stereotactic biopsy tissue for complex and integrated investigative multi-modal molecular analyses (‘Multi-omics”) in the context of GBM regional heterogeneity is not routinely performed, Most of the tissue is consumed with standard of care clinical testing and the amount and quality of remaining cells, particularly in the context of recurrent GBMs that have failed previous treatments, has not previously been shown to be amenable to complex analyses. Here we performed highly resolved multi-modal analysis methods including single cell RNA sequencing, spatial-transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonal analysis, and immunopeptidomics on needle biopsy cores obtained from a single patient during the same procedure. In a second patient, we analyzed multi-regional core biopsies to decipher spatially associated tissue and genomic variance. Finally in a separate cohort of patients we investigated the utility of stereotactic biopsies as a method for generating patient derived xenograft models. Dataset integration across modalities showed good correspondence between spatial modalities and revealed tumor and immune cell associated metabolic profiles and cell signalling pathways. In conclusion, stereotactic needle biopsy cores are of sufficient quality for the purposes of investigative biopsy and can generate multi-omics data, providing data rich insight into a patient’s disease to interrogate the tumor immune microenvironment.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Malignant Cell, Glioblastoma Multiforme Cell

DISEASE(S): Brain Glioblastoma Multiforme

SUBMITTER: Ryuhjin Ahn

LAB HEAD: Forest White

PROVIDER: PXD046857 | Pride | 2025-05-06

REPOSITORIES: Pride

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			Action	DRS
	BTC_P001_GlobalPhos_F.mzML	Mzml
	BTC_P001_GlobalPhos_F.mzid.gz	Mzid
	BTC_P001_GlobalPhos_F1.raw	Raw
	BTC_P001_GlobalPhos_F10.raw	Raw
	BTC_P001_GlobalPhos_F2.raw	Raw

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Investigative needle core biopsies support multimodal deep-data generation in glioblastoma.

Yu Kenny K H KKH Basu Sreyashi S Baquer Gerard G Ahn Ryuhjin R Gantchev Jennifer J Jindal Sonali S Regan Michael S MS Abou-Mrad Zaki Z Prabhu Michael C MC Williams Marc J MJ D'Souza Alicia D AD Malinowski Seth W SW Hopland Kelsey K Elhanati Yuval Y Stopka Sylwia A SA Stortchevoi Alexei A Couturier Charles C He Zhong Z Sun Jingjing J Chen Yulong Y Espejo Alexsandra B AB Chow Kin Hoe KH Yerrum Smitha S Kao Pei-Lun PL Kerrigan Brittany Parker BP Norberg Lisa L Nielsen Douglas D Puduvalli Vinay K VK Huse Jason J Beroukhim Rameen R Kim Betty Y S BYS Goswami Sangeeta S Boire Adrienne A Frisken Sarah S Cima Michael J MJ Holdhoff Matthias M Lucas Calixto-Hope G CG Bettegowda Chetan C Levine Stuart S SS Bale Tejus A TA Brennan Cameron C Reardon David A DA Lang Frederick F FF Chiocca E Antonio EA Ligon Keith L KL White Forest M FM Sharma Padmanee P Tabar Viviane V Agar Nathalie Y R NYR

Nature communications 20250428 1

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, pro ...[more]

PMID: 40295505

Similar Datasets

Project description:Glioblastoma, IDH wild type (GBM) is a primary brain cancer with a poor prognosis and few effective therapies. The ability to investigate the tumor and its microenvironment during treatment would greatly enhance understanding of disease response, progression and impact of therapeutics. Stereotactic needle core biopsies are routine surgical procedures performed primarily for tumor diagnosis. Use of these biopsies for investigations into tumor and microenvironmental responses to treatment is rarely performed but holds great potential to support therapeutic monitoring and understanding of tumor evolution. However, it is unclear whether needle core biopsies are sufficient for multi-omics analysis and tumor models. Here we test the depth of data generation possible from stereotactic needle core biopsy tissue in two separate patients. In the first patient with recurrent GBM we performed highly resolved multi-omics analyses including single cell RNA sequencing, spatial-transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics from biopsy tissue obtained from a single procedure. In a second patient we analyzed multi-regional core biopsies to decipher spatial and genomic variance and quantify intra and inter-sample heterogeneity. We also investigated the utility of stereotactic biopsies as a method for generating patient derived xenograft (PDX) models in a separate patient cohort. Dataset integration across modalities highlighted spatially mapped immune cell associated metabolic pathways, revealed poor correlation between RNA expression and the tumor MHC Class I immunopeptidome, and validated inferred cell-cell ligand receptor interactions. In conclusion, stereotactic needle biopsy cores are of sufficient quality to generate multi-omics data and PDX models, provide data rich insight into a patient’s disease process and tumor immune microenvironment and can be of value in evaluating treatment responses.