Single-cell sequencing reveal Renin-Angiotensin-System regulator patterns guide intercellular communication of tumor microenvironment that contribute to gastric cancer progression and immunotherapy

Abstract

Abstract Background The renin-angiotensin system (RAS), which is involved in this process, is well-known for its function in blood pressure regulation. In addition to a systemic RAS, the preponderance of target organs have a local RAS. Consequently, RAS hormones and receptors are expressed variably in various types of cancer, the heart, blood vessels, and kidneys. RASi therapy has recently demonstrated promise as a cancer treatment, despite a number of obvious adverse effects, such as hypotension. Consequently, it is essential to perceive how RAS functioned within the tumor microenvironment. Methods Single-cell RNA-seq data were acquired from gastric cancer (GC) tumor tissues, and nonnegative matrix factorization (NMF) was used to identify 16 RAS regulators. We evaluated the prognosis and immunological response of TME clusters using GC and Immunotherapy cohorts retrieved from a public repository. Results For each cell type (fibroblasts, myeloid cells, T cells, endothelial cells, and mast cells), two or three subclusters were identified based on similar biological processes and marker genes. A connection was discovered between RAS regulatory elements and the clinical and biological aspects of GC, and the pseudotime trajectory of the main TME cell types was also identified. The results of bulk sequencing indicate that these RAS-related TME cell subgroups have a significant immunological response in patients undergoing ICB therapy, especially in CAFs and Tregs, and have a high prognostic value for GC patients. Among the associations uncovered by CellChat's research was the fact that certain TME cell subgroups were associated with RAS. Further investigation revealed that MIF-(CD74 + CXCR4) and MIF-(CD74 + CD44) ligand receptors play a role in RAS-related subgroups' communication with TME cells. Conclusion Our research uncovered a previously unknown RAS pathway in the microenvironment of gastric cancer. This route has implications for both the progression of the disease and immunotherapy.