Integrated single-cell and bulk transcriptomics identify autophagy-related immune-suppressive subtypes and a prognostic signature in colorectal cancer

Background: Colorectal cancer still causes many cancer deaths, and patient outcomes differ a lot. The tumor microenvironment can shape tumor growth and treatment response. Autophagy is a cell recycling process linked to tumor survival and immune control, but its cell-type pattern in colorectal cancer tissue and its clinical meaning are not clear. We mapped autophagy activity across cell types, defined autophagy-based subtypes, and tested their value for risk stratification. Methods: functional experiments. Results: Autophagy activity varied across the tumor microenvironment. Malignant and stromal cells showed higher autophagy levels than immune cells. High-autophagy tumors showed stronger tumor-stroma interactions, weaker immune communication, and an immune-suppressive microenvironment. Using 47 prognostic autophagy-related genes, we identified four subtypes with different overall survival, genomic alteration patterns, stemness signatures, and immune landscapes. The prognostic model performed well across independent cohorts. GOLGA2 (Golgi autoantigen, golgin subfamily A member 2) was the top risk gene and was upregulated in tumor tissues. Functional assays showed that GOLGA2 promotes HCT116 cell proliferation and migration. Conclusion: , so it may warrant further study as a potential target.