Extracting Intercellular Signaling Network Of Cancer Tissues Using Ligand-Receptor Expression Patterns From Whole-Tumor And Single-Cell Transcriptomes

Many behaviors of cancer, such as progression, metastasis and drug resistance etc., cannot be fully understood by genetic mutations or intracellular signaling alone. Instead, they are emergent properties of cell community that forms a tumor. Studies of tumor heterogeneity reveal that many cancer behaviors critically depend on the intercellular communication mediated by secreted signaling ligands and their cognate receptors that take place between cancer cells and stromal cells. Owing to systematic cancer omics efforts, we studied such cell-cell interactions using data from cancer transcriptome database. We curated a list of more than 2,500 ligand-receptor pairs and developed a method to identify their enrichment in tumors from TCGA pancancer data and to build a cell interaction network from single-cell data for the case of melanoma. Using the specificity of the ligand-receptor interaction and their expressions measured in individual cells, we built a map of a cell-cell communication network which indicate what signal is exchanged between which cell types. Such networks establish a new formal phenotypes which are embodied by the cell communication structure - it may offer new opportunities to identify the molecular signatures which may influence cancer cell behaviors by changing cell population dynamics.