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Published on: May 31, 2020
Investigative needle core biopsies for multi-omics in Glioblastoma
Abstract:
Glioblastoma (GBM) is a primary brain cancer with an abysmal prognosis and few effective therapies. The ability to investigate the tumor microenvironment before and during treatment would greatly enhance both 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 role of investigative biopsies - tissue sampling for the purpose of understanding tumor microenvironmental responses to treatment using integrated multi-modal molecular analyses ('Multi-omics") has yet to be defined. Secondly, it is unknown whether comparatively small tissue samples from brain biopsies can yield sufficient information with such methods. Here we adapt stereotactic needle core biopsy tissue in two separate patients. In the first patient with recurrent GBM we performed highly resolved multi-omics analysis methods including single cell RNA sequencing, spatial-transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics from biopsy tissue that was obtained from a single procedure. In a second patient we analyzed multi-regional core biopsies to decipher spatial and genomic variance. We also investigated the utility of stereotactic biopsies as a method for generating patient derived xenograft models in a separate patient cohort. Dataset integration across modalities showed good correspondence between spatial modalities, highlighted immune cell associated metabolic pathways and revealed poor correlation between RNA expression and the tumor MHC Class I immunopeptidome. In conclusion, stereotactic needle biopsy cores are of sufficient quality to generate multi-omics data, provide data rich insight into a patient's disease process and tumor immune microenvironment and can be of value in evaluating treatment responses.
One Sentence Summary:
Integrative multi-omics analysis of stereotactic needle core biopsies in glioblastoma.
Insights
Stereotactic needle biopsies can provide sufficient tissue for comprehensive multi-omics analysis in glioblastoma (GBM). This approach offers valuable insights into the tumor microenvironment and treatment response, enhancing our understanding of this aggressive brain cancer.
Area of Science:
- Neuro-oncology
- Cancer Genomics
- Immunology
Background:
- Glioblastoma (GBM) is an aggressive brain cancer with limited treatment options.
- Understanding the tumor microenvironment is crucial for improving therapeutic strategies.
- The utility of stereotactic needle biopsies for multi-omics analysis in GBM is not well-defined.
Purpose of the Study:
- To evaluate the feasibility of using stereotactic needle core biopsies for comprehensive multi-omics analysis in glioblastoma patients.
- To assess the quality and information yield of biopsy tissue for integrated molecular analyses.
- To explore the potential of biopsies for generating patient-derived xenograft models.
Main Methods:
- Stereotactic needle core biopsies were performed on two glioblastoma patients.
- Advanced multi-omics techniques were applied, including single-cell RNA sequencing, spatial-transcriptomics, metabolomics, proteomics, and immunopeptidomics.
- Multi-regional biopsies were analyzed for spatial and genomic variations.
- The utility for patient-derived xenograft model generation was investigated.
Main Results:
- Stereotactic needle biopsy cores yielded sufficient high-quality tissue for extensive multi-omics data generation.
- Integrated analysis revealed good correspondence between spatial modalities and highlighted immune cell-associated metabolic pathways.
- A poor correlation was observed between RNA expression and the tumor MHC Class I immunopeptidome.
- Biopsies showed potential for generating patient-derived xenograft models.
Conclusions:
- Stereotactic needle biopsies are adequate for generating multi-omics data in glioblastoma.
- This approach provides rich insights into the patient's disease and tumor immune microenvironment.
- Biopsies can be valuable for assessing treatment responses and advancing GBM research.
