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

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, Parkinsons disease-1, vascular cell adhesion molecule 1 (VCAM-1), and tumor necrosis factor-alpha (TNF-) were the most significantly altered following CRT. Of these, albumin, CRP, GFAP, IL-6, VCAM-1, and TNF- 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- 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.