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ORIGINAL RESEARCH ARTICLE

Exploring serum inflammatory markers and the acute phase response in glioblastoma multiforme pre- and post-concurrent chemoradiation

Sarisha Jagasia1 ,  Jason Shephard1 ,  Erdal Tasci1 ,  Thomas Joyce1 ,  Shreya Chappidi1 ,  Theresa Cooley Zgela1 ,  Mary Sproull1 ,  Megan Mackey1 ,  Kevin Camphausen1 ,  Andra V. Krauze1*
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1 Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America
GPD 2024, 3(3), 3580 https://doi.org/10.36922/gpd.3580
Submitted: 6 May 2024 | Accepted: 10 July 2024 | Published: 10 September 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Glioblastoma multiforme (GBM) is the most common primary brain tumor, characterized by poor overall survival and near-universal recurrence due to rapid proliferation and treatment resistance. Inflammatory markers (i.e., cytokines and acute phase reactants [APRs]) have been studied in serum as potential biomarkers in GBM. However, the lack of serum data collected at multiple time points, particularly during treatment interventions, has limited the translation of these findings into clinical applications for monitoring treatment response. In this study, we analyzed a panel of 29 cultivated serum inflammatory markers employing serum from 109 individuals with pathology-proven GBM, collected both pre- and post-chemoradiation therapy (CRT). The goal was to determine the feasibility of measuring these serum markers in patient samples and to understand the effects of CRT on inflammatory biomarkers and signaling pathways. Among the proteins studied, albumin, C-reactive protein (CRP), glial fibrillary protein (GFAP), kininogen, interleukin (IL)-13, IL-1b, IL-10, Parkinson’s disease-1, vascular cell adhesion molecule 1 (VCAM-1), and tumor necrosis factor-alpha (TNF-α) were the most significantly altered following CRT. Of these, albumin, CRP, GFAP, IL-6, VCAM-1, and TNF-α emerged as the most relevant and promising serum biomarkers. Interaction analyses of baseline and post-CRT data identified IL-6 as a potential driver of signal alteration linked to APRs pathways and suggested its role as a mediator of tumor microenvironment reprogramming in conjunction with TNF-α and VCAM-1. The data revealed a balancing act of pro-apoptotic, anti-proliferative, and pro-viability pathways, with significant impacts on the signal transducer and activator of transcription 3 and nuclear factor kappa B pathways. Overall, the altered signature of the examined serum biomarkers suggests a decrease in the inflammatory response following GBM treatment. These findings underscore the need for further research, incorporating clinical outcomes and validation in larger datasets, to confirm the clinical applicability of these biomarkers.

Keywords
Serum
Proteomics
Biomarkers
Inflammation
Acute phase response
Glioblastoma
Funding
Funding is provided in part by the NCI NIH intramural program (ZID BC 010990).
Conflict of interest
The authors declare that they have no competing interests.
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