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Gene & Protein in Disease Exploring serum inflammatory biomarkers in GBM

A C

B D

Figure 4. 3D scatterplots visualizing protein interactions at baseline (A and B) and following CRT-induced alterations (C and D). (A and C) Acute phase
proteins (CRP, albumin) and GFAP. (B and D) IL-6, VCAM-1, and TNF-α. These scatter plots showcase six of the seven most significant markers (CRP,
albumin, GFAP, IL-6, VCAM-1, TNF-α), with IL-13 excluded due to its decreased interactions relative to IL-6, allowing for optimal visualization.
Abbreviations: CRT: Chemoradiation therapy; GFAP: Glial fibrillary protein; IL: Interleukin; TNF-α: Tumor necrosis factor alpha; VCAM-1: Vascular cell
adhesion molecule 1.

the expected decreased CRP/increased albumin trend are also reflected in the STRING network (Figure 5),
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does not hold true (yellow and orange dots); instead, these with VCAM-1, CRP, IL-13, IL-6, GFAP, and TNF being
patients exhibited increased CRP and decreased albumin highly interconnected and centrally connected to
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levels. In addition, GFAP alterations (predominantly albumin, supported by robust evidence in the literature.
decreased) showed variability not observed in the pre- In IPA, employing the observed signal alterations, major
CRT values. While pre-CRT levels of VCAM-1 and canonical pathways were identified, including acute
TNF-α in relation to IL-6 are relatively stable (Figure 4B), phase response (Figure 6A) and, notably, the tumor
post-CRT alterations in VCAM-1 (overall increased) microenvironment pathway (Figure 6B). Inflammation
and TNF-α (overall decreased) reveal an observable and inflammation-related pathways were overall
separation of signals within the patient population, with decreased, consistent with the observed alterations
subpopulations displaying elevated (yellow and orange in serum levels pre- versus post-CRT. The focus of the
dots) and decreased (purple) IL-6 levels (Figure 4D). signal centered on an overall decrease in inflammation
In summary, CRP, albumin, and VCAM-1 may serve as across all networks, particularly neuroinflammation. The
important biomarkers for both pre- and post-treatment APR pathway interaction identified in IPA employing
measurements in patients with GBM, while GFAP, IL-6, alteration (pre- versus post-CRT) data (Figure 6A)
and TNF-α might be more relevant when considering revealed IL-6 as a crucial mediator, with the potential to
treatment-induced alterations. capture robust protein signals in plasma. Corticosteroid
effects also emerged as a factor in this pathway. The tumor
3.3. Pathway analysis microenvironment pathway, using pre- versus post-CRT
Altered molecules pre- versus post-CRT were analyzed alteration data illustrated the potential downstream
using IPA to elucidate their mechanistic relationships effects of the proteins analyzed in serum, specifically
and relevant biological pathways. The associations for the those identified as statistically significant for alteration
seven most significant markers identified in this analysis and/or interaction (Figure 6B).

Volume 3 Issue 3 (2024) 7 doi: 10.36922/gpd.3580