Pan-cancer analyses of pyroptosis with functional implications for prognosis and immunotherapy in cancer

Background Programmed cell death is an active and orderly form of cell death regulated by intracellular genes that plays an important role in the normal occurrence and development of the immune system, and pyroptosis has been found to be involved in tumorigenesis and development. However, compressive analysis and biological regulation of pyroptosis genes are lacking in cancers. Methods Using data from The Cancer Genome Atlas, we established a score level model to quantify the pyroptosis level in cancer. Multiomics bioinformatic analyses were performed to assess pyroptosis-related molecular features and the 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 in different types of cancer, attributed to the CAN frequency and differences in DNA methylation levels. We established a pyroptosis level model and found that pyroptosis had dual roles across cancers, while the pyroptosis levels were different among multiple cancers and were significantly associated with clinical prognosis. The dual role of pyroptosis was also shown to affect immunotherapeutic efficacy in several cancers. Multiple pyroptosis genes showed close associations with drug sensitivity across cancers and may be considered therapeutic targets in cancer. Conclusions Our comprehensive analyses provide new insight into the functions of pyroptosis in the initiation, development, progression and treatment of cancers, suggesting corresponding prognostic and therapeutic utility.

Automated summary

Through comprehensive analysis, it was found that pyroptosis is aberrantly expressed in different types of cancer, attributed to CAN frequency and differences in DNA methylation levels. A pyroptosis level model was established, revealing a dual role of pyroptosis in cancers, with different levels across multiple cancers significantly associated with clinical prognosis.