Aggregate aggrephagy regulator patterns guide intercellular communication of tumor microenvironment that contribute to gastric cancer progression and immunotherapy

Abstract Background Aggregate autophagy plays a key role in cancer progression; however, how aggregate autophagy plays a role in tumor microenvironment (TME) remains to be elucidated. Methods 30571 single cells from the single-cell RNA-seq data of 13 gastric cancer (GC) specimens were analyzed by nonnegative matrix factorization (NMF) to find out the effects of 44 aggregate autophagy-related genes on major TME cells. The prognosis and immune response of TME clusters were determined using GC and immunotherapy cohorts from the public information base. Results Single-cell sequencing revealed that aggregate autophagy may be closely related to the clinical and biological characteristics of GC and the pseudo-time trajectories of major TME cell types. At the same time, NMF algorithm combined with Bulk-seq analysis to cluster cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), T cells and B cells, revealing that clusters regulated by different aggregates of autophagy-related genes have significant prognostic value in metabolism, prognosis and immune response in patients with gastric cancer. Finally, CellChat analysis showed that the aggregate autophagy-related cell subtypes of TME cells showed diversified and extensive interaction with tumor epithelial cells, and ligand-receptor pairs such as SPP1-CD44,MIF-CD74-CD44,MIF-CD74-CXCR4 mediated the communication between aggregate autophagy-related subtypes of TME cells and tumor epithelial cells. Conclusion Our study reveals for the first time that the tumor microenvironment mediated by aggregate autophagy regulates the intercellular communication in the process of GC development and anti-tumor immunoregulation.