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Gene & Protein in Disease Exploring serum inflammatory biomarkers in GBM

designs and the collection of serum samples at various time calcium levels are interpreted in conjunction with serum
points. While the SOMAScan® panel is not yet approved albumin levels. We consider that this principle applies
for diagnostic use, partly due to the lack of calibration, equally in the cases of GBM.
research continues to emerge with a growing number of In summary, even if normal ranges for the examined
proteins measured in newer versions of the panel, and markers were available, their interpretation would remain
its utility across various medical scenarios, including highly context-specific. While the lack of established
malignancies, is evolving. There remains a persistent normal ranges for these markers remains a critical issue,
need to link the values measured in the assay with those studies such as the current one add significant value, as
measured in clinical practice, though this presents several serum levels of these markers pre- and post-CRT in GBM
challenges due to the inherent variability in biological have not been described to date.
samples and the complexity of accurately quantifying a
vast array of proteins. We strongly encourage the ongoing evolution of non-
invasive biospecimen data and data sharing in this field.
Despite the absence of known normal ranges or The current inability to carry out validation complicates
standardized reference values for most of the markers in the interpretation of results, making it difficult to
this study, which represents a limitation, we consider the compare findings across different studies or to apply these
findings valuable given that the alterations in these markers findings toward diagnostic use. However, it is important
have not previously been described in GBM pre- versus to highlight that the data presented here are significant
post-SOC treatment. It is also important to note that, as in within the context of patients with pathology-proven
many scenarios encountered in clinical medicine, a serum GBM, all of whom underwent the same SOC management.
laboratory value does not necessarily need to be outside Despite ongoing challenges, rigorous validation efforts
the normal range to be clinically relevant, and an out-of- have been implemented to mitigate these issues. Studies
range value is not necessarily indicative of pathology.
have demonstrated the assay’s reliability through extensive
In GBM and glioma, more broadly, as in numerous cross-referencing and validation with established
other clinical contexts, values within the normal range can methodologies, ensuring that the data obtained are both
still provide important information by examining trends accurate and reproducible. 27,29,30,98 Although SOMAScan®
over time. For instance, a series of results within the normal is not approved for clinical use at this time, the assay has
range can indicate a trend, such as an increasing serum proven to be a robust and reliable platform for proteomic
creatinine level, which, even if still within the normal research, supporting its continued use in advancing our
range, can suggest declining kidney function. In addition, understanding of complex diseases like GBM. Future
gliomas represent a highly heterogeneous and rare disease, directions include growing clinically annotated serum
making it further expected that normal range values may proteomic data for clinically actionable markers such as
not be appropriate for all glioma patient populations and CRP, as most patients only have these values measured
that normal range values can still be compatible with the during acute events. Our future directions include the
presence of malignancy. For example, hemoglobin levels standard measurement of clinically implemented markers
measured in the clinic may vary between an adult man and in the study.
a pregnant woman, where a value at the upper or lower end
of the normal range might still be significant. 5. Conclusion
In the context of malignancy, there are several Both goals of the study were successfully met, as several
prominent biomarkers, such as CA-125 in ovarian cancer, inflammatory and acute phase response markers identified
where measured CA-125 values can be normal despite a as important to the diagnosis, grading, or treatment of
diagnosis of ovarian cancer. Similarly, SOC ranges for a glioma were measured in the serum of GBM patients several
thyroid panel are interpreted differently for thyroid cancer years after collection. These markers exhibited observable
patients compared to those with benign thyroid disease. alterations during SOC management and demonstrated
Furthermore, it is important to consider that individual significant mechanistic interactions linked to signaling
baseline values can vary, and a significant change from a pathways. Albumin, CRP, GFAP, IL-6, VCAM-1, and TNF
patient’s baseline, even if within the normal range, can be emerged as the most significant serum biomarkers. Although
meaningful. For example, a sudden drop in hemoglobin IL-6 was altered with SOC without achieving statistical
from a patient’s typical level might indicate bleeding or significance, it remains promising for several reasons:
another evolving pathological process. Finally, as is often (i) Markers that are altered but not statistically significant
the case in medicine, the interpretation of one test depends in initial analyses may achieve significance in larger
on the context of multiple tests. For example, serum cohorts with further analysis.

Volume 3 Issue 3 (2024) 12 doi: 10.36922/gpd.3580