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Gene & Protein in Disease Exploring serum inflammatory biomarkers in GBM

Albumin, CRP, and GFAP were measured at high levels positively associated with VCAM-1 both pre-CRT and
in serum in this study. All three have previously been with alteration post-CRT. CRP, in particular, interacted
examined preoperatively in the serum of GBM patients and extensively with several other markers, including
found to be associated with patient outcomes. 15,34,46 In this fibrinogen, IL-10, IL-1b, IL-6, PD-1, SAA, TNF-α, and
study, albumin levels generally increased, and CRP levels VCAM-1, indicating that its role as an APR may involve
generally decreased with treatment, which contrasts with significant mechanistic connections. Pathway analysis
the anticipated inflammatory response typically driven by identified IL-6 as a potential mediator in both the APR
chemotherapy, radiation, and the ensuing acute effects. pathway and the tumor microenvironment (Figure 6).
The observed alterations may be attributed to a decrease The lack of statistical significance in IL-6 alterations with
in marker levels following an initial post-operative peak, CRT is potentially attributable to its short plasma half-
which could also be influenced by the administration of life, or its varied biological role, as suggested (Figure 4D),
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corticosteroids. However, our analysis examined both where it appears to act differently across clinical contexts
the time from surgical resection and corticosteroid (e.g., elevated in some patients and decreased in others).
administration, and neither was significantly associated TNF-α, which also has a short half-life —potentially even
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with baseline or altered protein levels. It is also important shorter than IL-6—exhibited several interactions both pre-
to note that the half-life of several of these markers is CRT and with the alteration post-CRT, second only in the
quite short, often <24 h, making it unlikely that baseline number to CRP.
measurements would reflect surgical intervention that Overall, from a mechanistic standpoint, the observed
occurred 2 – 3 weeks earlier. The interplay between serum signature suggests that the acute phase response
corticosteroid administration and signaling pathway and inflammation pathways are decreased (Figure 6A),
alterations is complex and poorly understood. Previous driven by a rise in albumin and a decrease in CRP. The
studies in murine models have indicated an overall tumor microenvironment (Figure 6B) emerged as one of
reduction in inflammation, decreased NF-κB activity, the integral pathways associated with the serum proteins
and subsequently, a decrease in inflammatory cytokines analyzed in this analysis. The interplay between IL-6,
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such as IL-6, TNF-α, and IL-1b with corticosteroid STAT3, and NF-κB pathways was identified, revealing a
administration. This reduction in inflammation has bidirectional downstream effect of decreased proliferation
also been linked to adverse outcomes, partly attributed and tumor cell viability (driven through STAT3 and
to the administration of corticosteroids in individuals NF-κB). However, findings oppositional to the levels
with aggressive disease, potentially impacting the tumor of downstream molecules indicate complex dynamics,
microenvironment and interacting with CRT. It has been possibly reflecting both tumor response and resistance.
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suggested that corticosteroid-induced antiproliferative These findings suggest that signaling through STAT3
effects may contribute to protection from CRT-induced is decreased, possibly with TNF-α and CRP acting as
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genotoxic stress, suggesting that corticosteroids may mediators in response to CRT, while cell viability and
affect immune-related signaling and treatment response. resistance may be driven by increased levels of IL-6,
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Further analysis of albumin and CRP, along with markers VCAM-1, and KNG1. This interpretation aligns with the
such as NF-κB, may reveal clear linkages to clinical factors observed decrease in other proteins typically associated
or outcomes, particularly with validation in larger datasets.
with tumor persistence or progression (MMP9, SAA,
Among the altered proteins, several are of particular fibrinogen). KNG1, which was a strongly captured signal
importance in understanding the immune response in the panel and increased pre- versus post-CRT has an
of glioma, including albumin, VCAM-1, IL-10, 38,44 unclear role in glioma.
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IL-13, 51,53 GFAP, 15,48,49,65,82 TNF-α, 44,54,55 CRP, 25,26,32,45,46,52 and There are some discordant findings in this analysis,
IL-1b. PD-1 levels increased with CRT but did not exhibit particularly with IL-1b and VCAM-1. While the literature
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extensive interactions with other markers; however, given suggests that IL-1b induces the expression of VCAM-1, in
PD-1’s relevance in the field, further analysis with clinical this analysis, IL-1b was decreased, but VCAM-1 increased.
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markers may shed more light on its role in inflammation Similarly, IL-6 was overall increased pre- versus post-CRT,
and treatment response. although some literature evidence, such as the study by
Albumin is one of the most intriguing serum signals West et al., suggests that IL-6 levels would decrease with
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in this analysis. It exhibited the third-highest serum treatment. West et al. reviewed IL-6 and noted that its
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measurement level (Figure 1A) and showed a statistically role is evolving, with connections to tumor grade, stem
significance increase with CRT (Figure 1B). Albumin cell burden, and resistance to therapy. The interactions
was inversely associated with CRP, GFAP, and SAA, and between IL-6 and other markers in this study, including

Volume 3 Issue 3 (2024) 10 doi: 10.36922/gpd.3580