Background:Bladder cancer (BCa) is a highly prevalent disease with a poor prognosis. There is no better forecasting method for it yet. Current studies demonstrate that pyroptosis
is involved in the development and progression of various cancers.Methods:This study employed bioinformatics techniques to analyze the data of BCa patients obtained from the TCGA and GEO databases in order to construct a prognostic risk model. The
TCGA dataset was used for the training set, and the multiple external datasets (including
GSE13507, GSE31684, GSE48075, IMvigor210, and GSE32894) were applied as the validation
sets. Prognostic-associated pyroptosis genes screened by univariate Cox regression analysis were
utilized to construct the lasso Cox regression model. GO and KEGG analysis results identified
the selected genes that are primarily involved in the inflammation and cell death processes. The
related patients were grouped into low- and high-risk groups. Kaplan–Meier survival analysis
was performed to compare survival differences between the risk groups. The accuracy of this
risk prediction model was assessed by ROC. We also applied the Human Protein Atlas (HPA) to
detect the protein expression of these genes. Subsequently, qRT-PCR was performed to verify
the expression of these model genes.Results:There are 29 pyroptosis-related genes with significant expression differences between
BCa and corresponding adjacent tissues, and 11 genes (SH2D2A, CHMP4C, MRFAP1L1,
GBP2, EHBP1, RAD9A, ANXA1, TMEM109, HEYL, APOL2, ORMDL1) were picked by univariate and LASSO Cox regression analysis. Immunological cell infiltration and ssGSEA results
further indicated that the low and high-risk groups were substantially correlated with the immune
status of BCa patients. According to TCGA and multiple external datasets, Kaplan-Meier survival curves showed the overall survival rate of the high-risk group to be decreased. ROC curves
showed the model established to be accurate and reliable. Moreover, the HPA database also
demonstrated the verification of the modeled genes’ expression in BCa and normal bladder tissue using the HPA database. qRT-PCR results also suggested the up-regulated EHBP1 and
down-regulated RAD9A mRNA expression levels to be confirmed in 15 pairs of BCa and corresponding adjacent tissues.Conclusion:This study presents the development and validation of a novel gene signature associated with pyroptosis, which holds the potential for predicting patient outcomes in BCa and
providing insights into the immune microenvironment of BCa.
