Glioblastoma (GBM) is a common and highly malignant type of primary brain tumor. The tumor microenvironment (TME) is critical for better understanding the metabolic state of cells, and therefore the downstream effects on treatment, including chemotherapeutic agents.
Until now, spatial understanding of GBM metabolomic and lipidomic profiles have been limited by a lack of available research tools.
This poster highlights the latest mass spectrometry and spatial biology solutions for GBM tissue analysis, offering critical insights into the metabolic signatures and immune cell infiltration of this tissue type.
Download this poster to discover:
- A method of analysis that can reveal changes in lipid regulation for healthy vs disease-state
- Contextualizing traditional LC-MS with spatial information
- An innovative spatial biology workflow that can add meaningful spatial protein information
Germany 3Bruker Scientific LLC, Billerica, MA 01821, USA 4Instituteof Surgical Pathology, Faculty of Medicine –University of Freiburg, 79106 Freiburg, Germany For Research Use Only. Not for use in clinical diagnostic procedures. Conclusion Glioblastoma(GBM)isthemostcommonandahighlymalignantprimarybrain tumor,withfive-yearsurvivalratesbelow10%.GBMsarecharacterizedbyhigh levelsofheterogeneitywithinthetumorcellsandthetumormicroenvironment (TME),whichconsistsofbloodvesselsandnecroticcellsintermingledwith differentiatedandstem-like tumor cells. Tumor heterogeneity influences chemotherapyresistanceandlocalcancercelldissemination,bothconnected toahighrecurrencerateof>90%.Disruptioninmetabolismhasbeenreported inGBM,howeverincorporationofthespatialcontextthatallowsassessmentof theintratumorheterogeneityandTMEhavebeenstudiedminimally.Herewe showaSpatialOMxworkflowstartingwith4DLC-MS/MSlipidomics.The resultswerethenusedfor improvedannotationforthesubsequentMALDI Imagingexperiment.ThesecondMALDI Imagingexperimentonthesame tissueutilizedtheMALDIHiPLEX-IHCworkflowtodetectseveraldifferentintact proteinsontissueandoverlaythisinformationforbiochemicalcorrelation. FreshfrozentissuesectionsfromthreeGBMpatientsandoneastrocytoma patientwerefirsthomogenized,andlipidswereextractedviatert-methylbutyl ether(MTBE)phaseseparationandmeasuredviaLC-MS/MSonatimsTOFfleX. AfterwardsthetissuewasmeasuredviaMALDI ImagingandTIMSon, first acquiringinformationfromlipids,followedbytheantibodybasedMALDIHiPLEXIHC1workflow. ImageswereacquiredonatimsTOFfleXMALDI-2with20µm spatialresolutionwithTIMSionmobilityonforthelipidimaging.Metaboscape® wasusedforannotationofMALDIImagingdatausingm/zvaluesincombination withthemeasuredcollisionalcrosssectionsfromthe4DLipidomicsexperiment. MALDIHiPLEX-IHCwasperformedaccordingtotheAmberGenstainingprotocol withantibodiesspecificfortumor(GFAP,Vimentin,Ki67), immunecells, tumor microenvironment (CD68,CD4), aswell asageneral cell structuralmarker (Collagen1A1). Introduction Methods Figure1.Workflowschematic,startingwiththedifferenttissuetypes,GareGBMsamples andAareastrocytomasamples.Firstahomogenateofeachtissuewasgeneratedand4D Lipidomicswasperformed.ResultswereusedforannotationofalipidMALDIImaging run.Afterwardsmatrixwasremoved,andstainingperformedandasubsequentMALDI HiPLEX-IHCimagingrunwasperformedonthesametissuesection.
