Expression Analysis of Ligand-Receptor Pairs Identifies Cell-to-Cell Crosstalk between Macrophages and Tumor Cells in Lung Adenocarcinoma

Abstract

Background. Lung adenocarcinoma is one of the most commonly diagnosed malignancies worldwide. Macrophage plays crucial roles in the tumor microenvironment, but its autocrine network and communications with tumor cell are still unclear. Methods. We acquired single-cell RNA sequencing (scRNA-seq) ( $n=30$ ) and bulk RNA sequencing ( $n=1480$ ) samples of lung adenocarcinoma patients from previous literatures and publicly available databases. Various cell subtypes were identified, including macrophages. Differentially expressed ligand-receptor gene pairs were obtained to explore cell-to-cell communications between macrophages and tumor cells. Furthermore, a machine-learning predictive model based on ligand-receptor interactions was built and validated. Results. A total of 159,219 single cells (18,248 tumor cells and 29,520 macrophages) were selected in this study. We identified significantly correlated autocrine ligand-receptor gene pairs in tumor cells and macrophages, respectively. Furthermore, we explored the cell-to-cell communications between macrophages and tumor cells and detected significantly correlated ligand-receptor signaling pairs. We determined that some of the hub gene pairs were associated with patient prognosis and constructed a machine-learning model based on the intercellular interaction network. Conclusion. We revealed significant cell-to-cell communications (both autocrine and paracrine network) within macrophages and tumor cells in lung adenocarcinoma. Hub genes with prognostic significance in the network were also identified.