SIO: A Spatioimageomics Pipeline to Identify Prognostic Biomarkers Associated with the Ovarian Tumor Microenvironment

SIMPLE SUMMARY: High-grade serous ovarian cancer (HGSC) caused more than 13,000 deaths annually in the United States. A critically important component that influences the HGSC patient survival is the tumor microenvironment. However, how different cells interact to influence HGSC patients’ survival remains largely unknown. To investigate this, we developed a pipeline that combines imaging mass cytometry (IMC), location-specific transcriptomics, and deep learning to identify the distribution of various stromal, tumor and immune cells as well as their spatial relationship. Our pipeline automatically and accurately segments cells and extracts salient cellular features to identify biomarkers, and multiple nearest-neighbor interactions among different cells that coordinate to influence overall survival rates in HGSC patients. In addition, we integrated IMC data with microdissected tumor and stromal transcriptomes to identify novel signaling networks. These results may lead to the discovery of novel survival rate-modulating mechanisms in HGSC patients. ABSTRACT: Stromal and immune cells in the tumor microenvironment (TME) have been shown to directly affect high-grade serous ovarian cancer (HGSC) malignant phenotypes, however, how these cells interact to influence HGSC patients’ survival remains largely unknown. To investigate the cell-cell communication in such a complex TME, we developed a SpatioImageOmics (SIO) pipeline that combines imaging mass cytometry (IMC), location-specific transcriptomics, and deep learning to identify the distribution of various stromal, tumor and immune cells as well as their spatial relationship in TME. The SIO pipeline automatically and accurately segments cells and extracts salient cellular features to identify biomarkers, and multiple nearest-neighbor interactions among tumor, immune, and stromal cells that coordinate to influence overall survival rates in HGSC patients. In addition, SIO integrates IMC data with microdissected tumor and stromal transcriptomes from the same patients to identify novel signaling networks, which would lead to the discovery of novel survival rate-modulating mechanisms in HGSC patients.