biostudies-literatureTill JENational Center for Advancing Translational SciencesThe Steven Elek III GBM Research FundUniversity of Pennsylvania’s Institute for Translational Medicine and Therapeutics’ Transdisciplinary Program in Translational Medicine and TherapeuticsNCATS NIH HHSThe James and Marlene Scully Liquid Biopsy Innovation FundUniversity of Pennsylvania's Institute for Translational Medicine and Therapeutics' Transdisciplinary Program in Translational Medicine and TherapeuticsNational Center for Advancing Translational Sciences (NCATS)National Center for Advancing Translational Sciences of the NIH1292-1304https://www.ebi.ac.uk/biostudies/studies/S-EPMC11961315biostudies-literatureUnknown31(7)<h4>Purpose</h4>Noninvasive prognostic biomarkers to inform clinical decision-making are an urgent unmet need for the management of patients with glioblastoma (GBM). We previously showed that higher circulating cell-free DNA (ccfDNA) concentration is associated with worse survival in GBM. However, the biology underlying this is unknown.<h4>Experimental design</h4>We prospectively enrolled 129 patients with treatment-naïve GBM with blood drawn prior to initial resection (baseline) and at the time of the first postradiotherapy MRI. We performed ccfDNA methylation deconvolution to determine cellular sources of ccfDNA. ELISA was performed to detect citrullinated histone 3 (citH3), a marker of neutrophil extracellular traps (NET). Multiplex proteomic analysis was used to measure soluble inflammClinical cancer research : an official journal of the American Association for Cancer ResearchCorticosteroid-Dependent Association between Prognostic Peripheral Blood Cell-Free DNA Levels and Neutrophil-Mediated NETosis in Patients with Glioblastoma.PMC11961315UL1TR001878UL1 TR001878Macia CMansour MYazdani ZShah SSNabavizadeh AMcCoy ESnuderl MDesai ASBallinger DPatel TBagley SJSeewald NJSamberg HBochenek VWang ZDandu SPrior TBinder ZAAbdalla AZhou WGollomp KCarpenter ELPhillips REO'Rourke DMSerrano JAmankulor NMWills CAYin MTill JEfalseCorticosteroid-Dependent Association between Prognostic Peripheral Blood Cell-Free DNA Levels and Neutrophil-Mediated NETosis in Patients with Glioblastoma.<h4>Purpose</h4>Noninvasive prognostic biomarkers to inform clinical decision-making are an urgent unmet need for the management of patients with glioblastoma (GBM). We previously showed that higher circulating cell-free DNA (ccfDNA) concentration is associated with worse survival in GBM. However, the biology underlying this is unknown.<h4>Experimental design</h4>We prospectively enrolled 129 patients with treatment-naïve GBM with blood drawn prior to initial resection (baseline) and at the time of the first postradiotherapy MRI. We performed ccfDNA methylation deconvolution to determine cellular sources of ccfDNA. ELISA was performed to detect citrullinated histone 3 (citH3), a marker of neutrophil extracellular traps (NET). Multiplex proteomic analysis was used to measure soluble inflamm2025-01-01T00:00:00Z2025 Apr2026-06-04T01:45:31.839Z2026-05-04T03:13:41.208ZS-EPMC119613153988726410.1158/1078-0432.ccr-24-316910.1158/1078-0432.CCR-24-3169