Article Describes Gene Signature Ratio that Predicts Survival in Colon Cancer

Biotech Support Group (BSG) and Leiden University Medical Center (LUMC), Leiden, The Netherlands, announce publication of a journal article in the publication Cancers. It is based upon on their joint goal to correlate BSG’s patent pending Stroma Liquid Biopsy™ panel of blood-borne biomarkers, to tissue derived tumor-stroma ratio (TSR) scoring methods developed by LUMC. The citation is:

Ravensbergen, Cor J., et al. "The Stroma Liquid Biopsy Panel Contains a Stromal-Epithelial Gene Signature Ratio That Is Associated with the Histologic Tumor-Stroma Ratio and Predicts Survival in Colon Cancer." Cancers 14.1 (2022): 163.

Liquid biopsy has emerged as a novel approach to tumor characterization, offering advantages in sample accessibility and tissue heterogeneity. However, as mutational analysis predominates, the tumor microenvironment has largely remained unacknowledged in liquid biopsy research. The Stroma Liquid Biopsy™ (SLB) proteomics panel comprises a set of 13 proteins from interconnected stromal pathways (i.e., coagulation, complement, acute phase inflammation) and is believed to capture a plasma proteomic blueprint indicative of a deranged systemic response in cancer. As such, it encompasses the importance of the tumor microenvironment (TME) compartment in liquid biopsy. Within similar context, the histologic tumor-stroma ratio (TSR), a stroma-derived biomarker developed by LUMC, has been validated as an independent predictor of patient survival in various primary tumor types. The current work provides an explorative gene transcriptomic characterization of the SLB proteomics panel in colon carcinoma by integrating single-cell and bulk transcriptomics data from publicly available repositories.

The Stromal-Epithelial Gene Signature Ratio, is based on genes from the SLB panel, and classified by their expression as being derived from stromal-phenotypic or epithelial-phenotypic cells. In this way, it is demonstrated that histologic high stromal content is accompanied by increased gene expression of stroma-associated pathways in comparison to tumors with low stromal content. The gene signature ratio described in this study was found to be related to previous investigations of TSR and demonstrated a remarkably similar prognostic performance. These findings provide further molecular evidence for the prognostic power of the tumor stroma in clinical practice.

In addition to patient prognosis, high gene signature ratio-risk scores were associated with an increased proportion of Microsatellite instability (MSI) in comparison to low ratio-risk scores. Given the increased proportion of MSI in the high ratio risk score group, the signature ratio might be predictive of immune checkpoint inhibitor (ICI) therapy response in colon cancer and should be the subject of future studies in ICI therapy-treated patient cohorts.

The current report provides a first theoretical framework for proteomic signatures to potentially serve as an indicator for tumor-stroma content when applied in liquid biopsy. Ultimately, the stromal conditioning protein blueprint, as captured by the SLB panel, may provide a more refined stratification of the tumor and patient prognosis, and offer new insights into therapeutic strategies that might beneficially modulate the tumor-microenvironment.

“This is a very exciting article to have published, as LUMC has been at the forefront in research on the microenvironment componentry of cancer. While most cancer research is focused on genomic mutations, even with the introduction of immuno-therapies, we still know very little about individualistic hospitality to uncontrolled cellular proliferation. So BSG set out to answer whether stromal conditioning was measurable in blood sera, to most if not all cancers, regardless of primary tumor, stage, or metastatic disease. This discovery research led to our patent pending panel of Stroma Liquid Biopsy™ proteomic biomarkers. Now, the genes from this panel have been investigated here in this very compelling journal article. This validates the usefulness and potential clinical utility for liquid biopsy and proteomic characterization of stromal conditioning in cancer, as a further way to stratify patients towards the best treatment options.” states Swapan Roy, Ph.D., President and Founder of Biotech Support Group.

Lead authors Dr.Wilma Mesker (Associate Professor) and Cor Ravensbergen (Senior Medical Student) of the Leiden University Medical Center concur, and state further that, “the tumor-stroma microenvironment is an important prognostic parameter for patients with epithelial cancer types. However, tissue staining provides only qualitative information and does not offer any insight into specific cellular or protein mechanisms that impact survival. We do know that patients with a high amount of stromal cells in the primary tumor have a bad prognosis and respond worse to current chemo-, radio- and/or immunotherapy regimens. Now with the help of BSG’s Stroma Liquid Biopsy™ panel, our working hypothesis is showing real evidence for how stromal conditioning impacts survival. We will soon start our LC-MS analysis of the Stroma Liquid Biopsy™ protein panel on patient sera. From this analysis, we can envision future therapeutic strategies that can potentially modulate the tumor microenvironment, as the tumor-stroma ratio was found to be associated with pathologic response to neoadjuvant therapy. This supports the notion that the tumor microenvironment affects therapeutic response. So, we can begin to think about how modulation of stromal conditioning might improve immuno-oncology treatments, for example turning ‘cold’ tumors to ‘hot’. Consequently, we are very excited about the prospects for bridging the histologic tumor-stroma ratio with biomarkers for systemic response, as reported by the blood-based Stroma Liquid Biopsy™ panel.”