Pan-cancer analyses reveal cancer-type-specific autophagy signatures with potential implications for prognosis and therapy response

Autophagy is a common cellular degradation and recycling process that plays crucial roles in the development, progression, immune regulation, and prognosis of various cancers. However, a systematic assessment of the autophagy-related genes (ATGs) across cancer types is deficient. Here, a transcriptome-based pan-cancer analysis of autophagy with potential implications in prognosis and therapy response was performed. About 3 - 32 % of ATGs expressed differentially across 21 human cancers, and the autophagy-related score (ATS) based on differential ATGs could be used to predict the prognosis in 11 cancers, which was validated in multiple independent datasets. Autophagy was found to influence tumor immune microenvironment mainly by regulating tumor-infiltrating lymphocytes and myeloid-derived cells, and interactions between T cells and macrophages with lower ATS was enhanced to improve clinical outcomes by single cell analysis in bladder urothelial carcinoma (BLCA). In addition, the ATS was correlated with drug sensitivity and showed a capacity for prediction of therapy response in diverse cancers. Altogether, the results highlighted robust value of autophagy in cancer prognosis and treatment.