AGBT 2024 Poster: Identifying cancer neighborhoods and cancer-associated fibroblasts in prostate cancer using MERFISH

Abstract: 

Understanding the spatial complexities within cancer provides crucial information for evaluating individual tumor development and progression; recent research in prostate cancer has shown how critical it is for oncologists to maintain a spatial context while characterizing a highly heterogeneous tumor microenvironment. As more and more research groups acknowledge the need for spatial biology solutions to solve difficult questions surrounding cell identity, heterogeneity, and interaction, the Vizgen® MERSCOPE® Platform provides a powerful tool to illuminate spatial information. Built on Multiplexed Error-Robust Fluorescence in situ Hybridization (MERFISH) technology, MERSCOPE enables the direct profiling of the spatial organization of intact tissue with subcellular resolution. Here, we use a 500-gene panel to demonstrate the MERSCOPE® Platform’s spatial capability, assessing the canonical signaling pathways of cancer, cancer type-specific genes, select immune genes, proto-oncogenes, and tumor-suppressor genes in patient-derived prostate cancer samples. We found that MERFISH data correlate well with bulk-RNA seq from the same tissue. We were also able to directly profile the in situ expression of marker genes for cancer cells, fibroblasts, immune cells, and endothelial cells. Using the MERSCOPE Cell Boundary Stain kit, we were able to generate a molecular and cellular atlas of these individual patient tumors by clustering cells based on gene expression and mapping these clusters back onto a spatial representation of the tumor. We identified multiple cancer clusters with distinct gene expression profiles and spatial distributions. Using an alpha shape approach, we marked fibroblasts in the vicinity of cancer neighborhoods (cancer-associated fibroblasts, or CAFs). We identified upregulated genes in CAFs using our MERFISH gene panel as well as Tangram imputation of genome-wide single-cell expression data, which revealed upregulation of genes related to the extracellular matrix and tumorigenesis. These findings demonstrate how the MERSCOPE Platform can provide deep insights into the complex heterogeneity observed in the tumor microenvironment.*

*RUO only, not approved for diagnostic or therapeutic purposes