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Gene & Protein in Disease Exploring serum inflammatory biomarkers in GBM

leading to the identification of several biologically
relevant interactions.
(iii) Pathway analysis revealed an overall decrease in
inflammation following treatment, with a notable
duality of mechanistic interaction between Signal
transducer and activator of transcription 3 (STAT3)
and NF-κB, with IL-6 emerging as a potential mediator
of downstream effects.
Markers strongly supported by the literature were all
measurable and altered with treatment in patient serum,
despite the wide range of specimen collection dates (2005
– 2023) and considerable variations in the time between
sample collection and analysis. This consistency highlights
the robustness of the serum signals observed.
The major APRs include CRP, serum amyloid P
component, and SAA protein. These proteins are
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regulated by inflammatory cytokines, including IL-6,
Figure 5. Serum inflammatory biomarker networks and pathway IL-1, IL-1b, and TNF. Some proteins, known as negative
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associations for the most significantly altered markers, albumin and acute phase proteins (e.g., albumin), decrease during
GFAP, and the five additional markers (CRP, IL-13, IL-6, TNF, VCAM-1)
that exhibited more than 22 statistically significant (P < 0.05) interactions inflammatory processes, while others, termed positive
pre-CRT and with the alteration pre- versus post-CRT. STRING acute phase proteins (e.g., CRP), increase during such
interaction framework was employed, utilizing all interaction sources events. We focused particularly on albumin and CRP
with line thickness indicating the strength of data support. 14 measurements, as these are classical plasma proteins
Abbreviations: ALB: Albumin; CRP: C-reactive protein; GFAP: Glial already implemented clinically. Their interaction with
fibrillary protein; IL: Interleukin; TNF: Tumor necrosis factor;
VCAM-1: Vascular cell adhesion molecule. GFAP could potentially foster linkages to other serum
signals that may be specific to brain and tumor burden.
4. Discussion CRP has been studied as a marker in inflammatory
and infectious conditions, including stroke, diabetes,
Investigating inflammatory and acute phase response neurodegenerative disorders, and malignancies. 26,79 It has
serum biomarkers in malignancies, specifically in GBM, been investigated as a marker of both acute and chronic
presents significant challenges due to their lack of specificity inflammation, associated with fibrosis, aging, and
and the scarcity of literature correlating them with tumor neurodegeneration. In general, increased levels serve as a
grade and prognosis. The challenges are compounded risk indicator of poor prognosis. Serum albumin is the
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44
80
by factors such as the administration of corticosteroids most commonly employed as a nutritional marker, and in
and CRT, which can significantly confound results. cancer, low levels have been linked to poor outcomes. 28,29,81
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Additional confounding factors include the administration Albumin is also notably associated with anorexia-
of medications aimed at treating seizures, depression, cachexia syndrome and paraneoplastic manifestations
nausea, vomiting, and constipation. of malignancy. However, these associations are typically
weaker in primary brain tumors, which do not metastasize
To the best of our knowledge, this is the first study outside the brain and less frequently result in nutritional
to report on serum measurements of inflammatory deficiencies. The interplay between albumin and CRP has
biomarkers before and after SOC CRT in GBM. The been widely studied, including in GBM. GFAP has been
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significance of the data is assessed as follows: studied in several neurodegenerative and neurological
(i) We identified serum inflammatory markers that have conditions and in brain tumors, including glioma, as
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previously been associated with glioma and found that both a biomarker and potential therapeutic target. 47,48,82,83
several of these markers present strong serum signals Serum GFAP measurements have been associated with
and are altered with treatment in GBM, independent tumor invasion and migration. While GFAP has isoforms
of corticosteroids administration or the time following that are differentially expressed, a decrease in GFAP, as
surgical resection. observed in our study, has been associated with increased
(ii) The availability of 2 time points for measurement migratory capacity. The challenge with GFAP remains
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allowed us to explore the interactions among these the lack of clarity regarding which isoforms are measured
markers before and after therapeutic intervention, in various multiplex assays, including the one used in

Volume 3 Issue 3 (2024) 8 doi: 10.36922/gpd.3580