Identification of a Pyroptosis-Related Gene Signature and Effect of Silencing the and in Pancreatic Adenocarcinoma.

BACKGROUND

Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with an extremely poor prognosis. Pyroptosis has been demonstrated to play an important role in tumor prognosis. However, the expression of pyroptosis-related genes in PAAD and their correlations with prognosis remains unclear.

METHODS

In this study, the 36 pyroptosis-related genes that were differentially expressed between normal pancreatic tissues and PAAD tissues were identified via the "limma" R package. Based on these differentially expressed genes (DEGs), a five-gene signature was established by applying the least absolute shrinkage and selection operator Cox regression in the TCGA cohort and was validated in the GEO cohort. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of DEGs based on the risk model indicated that immune-associated biological processes and pathways were enriched. In vivo, we detected the expressions of and by immunohistochemistry in tumor tissues and adjacent normal tissues. In vitro, we silenced and to explore their effects on pancreatic cancer cells.

RESULTS

PAAD patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group. The expressions of and in tumor tissue were higher than those in the adjacent normal tissues in vivo. The knockdown of CASP4 significantly inhibited the invasion and migration but not the proliferation of PANC-1 cells. The knockdown of obviously inhibited the proliferation, migration, and invasion of PANC-1 cells.

CONCLUSION

Pyroptosis-related genes play important roles in predicting the prognosis of PAAD, and and affect the metastasis of PAAD.