News
Release
A
Mini-Review Describes the Analytical Aspects of Liquid
chromatography – Mass spectrometry (LC-MS) Methods Aimed at
Quantification of Stroma Liquid Biopsy™ Proteins in Body Fluids
MONMOUTH
JUNCTION, NJ, January
9, 2023 -- Biotech Support Group (BSG) reports on joint publication
with authors from research collaborators at Leiden
University Medical Center,
describing
the developmental and analytical aspects of
Tier 2 LC-MRM-MS protein quantification methods for liquid biopsies,
with a special focus on BSG’s Stroma Liquid Biopsy™ protein
panel. The
citation is:
N.
Diederiks, C.J. Ravensbergen, M. Treep, M. van Wezel, M. Kuruc, L.
Renee Ruhaak, R.A.E. Tollenaar, C.M. Cobbaert, Y.E.M. van der Burgt,
W.E. Mesker, Development
of Tier 2 LC-MRM-MS protein quantification methods for liquid
biopsies,
Journal of Mass Spectrometry and Advances in the Clinical Lab (2022),
https://doi.org/10.1016/j.jmsacl.2022.12.007
In
the pursuit of personalized diagnostics and tailored treatments,
quantitative protein tests contribute to a more precise definition of
health and disease, driven by unmet clinical needs. Internationally
standardized TNM classifications of malignant tumors are beneficial
for diagnosis, however treatment outcome and survival of cancer
patients is poorly predicted. To this end, the importance of the
tumor microenvironment (TME) has endorsed the introduction of the
tumor-stroma ratio as a prognostic parameter in solid primary tumor
types, determined via routine diagnostic pathology slides. However,
with the development of liquid chromatography – mass spectrometry
(LC-MS) methods we aim at quantification of tumor-stroma specific
proteins in body fluids, as the TME comprises a dynamic ecosystem of
cellular and subcellular interactions that surrounds malignant cells,
essential to tumor progression. The article states “Despite
significant advances in malignant cell-derived biomarkers, such as
circulating tumor cells (CTCs) and circulating cell-free tumor DNA
(ctDNA), the TME has remained surprisingly underappreciated in
current liquid biopsy research. To address TME profiling in liquid
biopsy, the Stroma Liquid Biopsy™ (SLB) panel was developed as an
experimental stroma-oriented proteomics alternative to the
conventional genomic liquid biopsy biomarkers in oncology”.
“The
SLB panel comprises a set of key proteins in interconnected stromal
pathways (e.g. coagulation, acute phase inflammation) and is believed
to capture a deranged systemic response to the presence of cancer in
a plasma proteome blueprint. Remarkably, we recently demonstrated
that the representing genes of the SLB protein panel compose
expression signatures that are expressed in malignant cells and the
non-malignant cells within the TME in colon cancer. Plasma protein
levels of the SLB panel may, therefore, reflect histologic
intratumoral stromal content and provide valuable prognostic
information in liquid biopsies.”. A Tier 2 liquid chromatography
multiple reaction monitoring mass spectrometry (LC-MRM-MS) assay, to
identify and quantify proteins from the SLB panel requires
well-defined selectivity, repeatability, sensitivity, and
reproducibility and is the optimal choice for analytical performance
of potential biomarkers. In
this mini-review the analytical aspect of this developmental
trajectory is further detailed.
Aims
and key objectives of the BSG – Leiden Research Collaboration
Tumors
are more than just a mass of proliferating cells and therefore cancer
progression is influenced by the multiple normal non-cancerous cell
types and networks of proteins dynamically interacting in active
tumorigenesis. These are not simply passive bystanders and
consequently reflect the tumor-associated microenvironments called
the stroma. Percolating through the tumor mass and introduced into
the general circulation, stromal conditioning of tumors can thus be
monitored by blood tests. Accounting for and characterizing the
stromal influence on disease progression and response to therapies
will become of paramount importance in the management of cancer
patients in the future.
Based
on stained surgically removed primary tissue sections, LUMC has
developed a tumor-stroma ratio (TSR) reported to be a strong,
independent prognostic parameter linking tumors with high stromal
content to poor prognosis in
multiple solid primary tumor types. In addition to patient prognosis,
the TSR was reported to predict response to neoadjuvant therapy in
breast and
gastrointestinal
cancers. Lastly, the combined assessment of the TSR and histologic
tumor immune cell infiltrate was recently suggested as a novel tool
in predicting response to checkpoint inhibitor therapy in colon
cancer. These reports support the notion of the TME as a valuable
addition to current diagnostics in clinical oncology. Given the lack
of TME parameters in cancer staging and grading classifications, the
TSR is currently subjected to prospective validation in colon cancer
in the international UNITED trial.
The
patent pending panel of BSG’s Stroma Liquid Biopsy™ proteomic
biomarkers, in part reflects the tumor-associated microenvironments
introduced into the bloodstream, and to which can be monitored by
blood tests. In this project, we aim to characterize and quantify the
Stroma Liquid Biopsy™ biomarkers from LUMC collected patient sera,
so as to correlate to the LUMC developed Tumor-Stroma Ratio scoring
methods. Once achieved, we will have gained invaluable information
central to understanding how individuals uniquely adapt to the
presence of cancer anywhere in the body, how individuals can be
stratified towards the best therapeutic options, and how individuals
uniquely respond to medical intervention.
To
Learn More About Tumour-Stroma Ratio, visit:
http://www.watchstroma.com
To
Learn More About Stroma Liquid Biopsy™, download whitepaper at:
StromaLiquidBiopsyWhitepaper02162022.pdf
(biotechsupportgroup.com)
About
Biotech Support Group LLC
Converging
with cultural and technological disruptions forthcoming in
healthcare, Biotech Support Group develops methods for cost effective
and efficient sample prep essential for these expanding markets.
Following a tiered business strategy, the company continues its
growth in the consumable research products area supporting the
rapidly expanding installation of LC-MS instrument and computational
infrastructure. For this market, key products include: AlbuVoid™
and AlbuSorb™ for albumin depletion, Cleanascite™ for lipid
adsorption, and HemogloBind™ and HemoVoid™ for hemoglobin
removal. From these innovations, the company has acquired
knowledgebase and biomarker intellectual property assets that support
discoveries of protein markers from blood, with special emphasis on
early detection and personalized medical decisions for cancer
patients. For more information, go
to https://www.biotechsupportgroup.com/Default.asp
For
business development at BSG,
Contact: Matthew
Kuruc 732-274-2866, mkuruc@biotechsupportgroup.com
About
Leiden University Medical Center (LUMC)
As
the world changes and its population ages, the
number of patients with chronic diseases and disorders is expanding,
while medical costs increase. Therefore, the health of the global
population is one of the biggest challenges of our time. Leiden
University Medical Center believes that this challenge asks for a
clear vision and mission. At the LUMC, students are trained in
lifelong innovation and learning. Researchers let themselves be
inspired and test their findings directly in practice. Patients can
count on being helped according to the state-of-the-art in science.
The LUMC believes in curing but also in prevention. By collaborating
with companies and organizations inside and outside the region, the
LUMC makes innovations and new applications actually possible. Thus
the LUMC serves as an innovator for improving healthcare science and
consequently people’s health. For more information, go
to https://www.lumc.nl
Keywords: Stroma
Liquid Biopsy™, Tier
2 LC-MRM-MS, Tumor
Microenvironment (TME), Tumor-Stroma
Ratio (TSR), Cancer patient
prognosis, predicting response to checkpoint inhibitor therapy
