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