Pan-Cancer Analyses of Pyroptosis With Functional Implications in Prognosis and Immunotherapy in Cancer

Abstract Background Programmed cell death is an active and orderly form of cell death regulated by intracellular genes, which plays an important role in the normal occurrence and development of the immune system, and pyroptosis has been found to be involved in the tumorigenesis and development. However, compressive analysis and biological regulation about pyroptosis genes are lack in cancers. Methods Using the data from the The Cancer Genome Atlas, we established a score level model to quantify the pyroptosis level of cancer. Multi-omics bioinformatical analyses was performed to detect pyroptosis-related molecular features and effect of pyroptosis on immunotherapy in cancer. Results In the present study, we performed a comprehensive analysis of pyroptosis and its regulator genes in cancers. Most pyroptosis genes were aberrantly expressed among different cancer types, which is contributed by the CAN frequency and differences of DNA methylation level in cancer. We established the modeling of the pyroptosis level and found that pyroptosis showed dual roles across cancers, while the pyroptosis levels were different in multiple and be significantly associated with clinical prognosis. The dual role of pyroptosis also affect the effects of immunotherapy in several cancers. Multiple pyroptosis genes showed close connections with drug sensitivity across cancers, and may be considered as therapy targets in cancer. Conclusions Our comprehensive analyses provide new insight into the functions of pyroptosis in the initiation, development, and progression and treatment across cancers, suggesting corresponding prognostic and therapeutic utility.