Longitudinal plasma protein profiling in glioblastoma patients using NULISAseq reveals treatment-associated changes across radiation and chemotherapy
7 affiliations
- 1Department of Internal Medicine, Section of Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Biotech Place, 3E-031, Winston-Salem, NC 27101 USA
- 2Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC 27157 USA
- 3Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157 USA
- 4Translational Neuroscience, Wake Forest University School of Medicine, Winston-Salem, NC 27157 USA
- 5Department of Psychiatry, Atrium Health Wake Forest Baptist, Medical Center Boulevard, Winston-Salem, NC 27157 USA
- 6Department of Neurology, Atrium Health Wake Forest Baptist, Medical Center Boulevard, Winston-Salem, NC 27157 USA
- 7Department of Cancer Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157 USA
Abstract
Purpose: Glioblastoma (GBM) is the most aggressive primary brain tumor with poor outcomes despite surgery, radiotherapy (RT), and temozolomide (TMZ). Monitoring relies on imaging, which is confounded by pseudoprogression and provides limited molecular insight. Circulating biomarkers may offer a minimally invasive approach to track disease and treatment effects.
Methods: We performed targeted longitudinal proteomic profiling of plasma from post-surgery GBM patients (n = 11) at baseline (pre-radiotherapy (RT)), after RT with concomitant TMZ, and after adjuvant TMZ, alongside healthy controls (n = 15), using the NULISAseq CNS panel covering 131 proteins related to neurodegeneration, neuroinflammation, and vascular health. Differential expressions were assessed using volcano plots, hierarchical clustering, paired statistical comparisons and longitudinal trends analysis.
Results: At baseline, GBM plasma showed elevated markers of neuroaxonal and glial injury, extracellular matrix regulators, and inflammatory signaling compared to controls. Several established neurodegeneration and Alzheimer’s disease- related biomarkers were also higher in GBM plasma versus controls. Following radiotherapy and concomitant TMZ, cytokines including IL10, IL5, and IL33 increased, indicating systemic immune activation, while BDNF showed a modest decline. Adjuvant TMZ treatment attenuated radiotherapy-induced cytokine elevations and reduced neuronal injury markers, suggesting therapy-driven reduction of inflammatory and neurodegenerative signals. Longitudinal analysis confirmed dynamic shifts in specific proteins across baseline, radiotherapy, and TMZ phases.
Conclusion: High-sensitivity plasma proteomics suggested therapy-induced changes in CNS-specific and immune markers in GBM, highlighting candidate biomarkers that can be further developed for real-time monitoring of treatment response. These findings suggest candidate circulating markers that may complement imaging for monitoring disease biology and therapeutic response, and warrant validation in larger cohorts.
Supplementary information: The online version contains supplementary material available at https://doi.org/10.1007/s11060-026-05839-2.
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BibTeX
@article{kumar2026longitudinal,
title = {{Longitudinal plasma protein profiling in glioblastoma patients using NULISAseq reveals treatment-associated changes across radiation and chemotherapy}},
author = {Ashish Kumar and Yangen He and Susy Kim and Fang-Chi Hsu and Christina S. Meade and Drew D. Kiraly and Roy Strowd and Glenn J. Lesser and Gagan Deep},
journal = {Journal of Neuro-Oncology},
year = {2026},
month = oct,
doi = {10.1007/s11060-026-05839-2},
url = {https://doi.org/10.1007/s11060-026-05839-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Longitudinal plasma protein profiling in glioblastoma patients using NULISAseq reveals treatment-associated changes across radiation and chemotherapy
AU - Ashish Kumar
AU - Yangen He
AU - Susy Kim
AU - Fang-Chi Hsu
AU - Christina S. Meade
AU - Drew D. Kiraly
AU - Roy Strowd
AU - Glenn J. Lesser
AU - Gagan Deep
PY - 2026
DA - 2026/10/31
JO - Journal of Neuro-Oncology
DO - 10.1007/s11060-026-05839-2
UR - https://doi.org/10.1007/s11060-026-05839-2
AB - Purpose: Glioblastoma (GBM) is the most aggressive primary brain tumor with poor outcomes despite surgery, radiotherapy (RT), and temozolomide (TMZ). Monitoring relies on imaging, which is confounded by pseudoprogression and provides limited molecular insight. Circulating biomarkers may offer a minimally invasive approach to track disease and treatment effects. Methods: We performed targeted longitudinal proteomic profiling of plasma from post-surgery GBM patients (n = 11) at baseline (pre-radiotherapy (RT)), after RT with concomitant TMZ, and after adjuvant TMZ, alongside healthy controls (n = 15), using the NULISAseq CNS panel covering 131 proteins related to neurodegeneration, neuroinflammation, and vascular health. Differential expressions were assessed using volcano plots, hierarchical clustering, paired statistical comparisons and longitudinal trends analysis. Results: At baseline, GBM plasma showed elevated markers of neuroaxonal and glial injury, extracellular matrix regulators, and inflammatory signaling compared to controls. Several established neurodegeneration and Alzheimer’s disease- related biomarkers were also higher in GBM plasma versus controls. Following radiotherapy and concomitant TMZ, cytokines including IL10, IL5, and IL33 increased, indicating systemic immune activation, while BDNF showed a modest decline. Adjuvant TMZ treatment attenuated radiotherapy-induced cytokine elevations and reduced neuronal injury markers, suggesting therapy-driven reduction of inflammatory and neurodegenerative signals. Longitudinal analysis confirmed dynamic shifts in specific proteins across baseline, radiotherapy, and TMZ phases. Conclusion: High-sensitivity plasma proteomics suggested therapy-induced changes in CNS-specific and immune markers in GBM, highlighting candidate biomarkers that can be further developed for real-time monitoring of treatment response. These findings suggest candidate circulating markers that may complement imaging for monitoring disease biology and therapeutic response, and warrant validation in larger cohorts. Supplementary information: The online version contains supplementary material available at https://doi.org/10.1007/s11060-026-05839-2.
SN - 0167-594X
SN - 1573-7373
ER -