Prognostic implications of a four-gene signature in non-muscle invasive bladder cancer

Abstract The high recurrence rate of non-muscle invasive bladder cancer (NMIBC) is a non-negligible problem in a clinical setting. Therefore, it is important to explore the affecting factors and to identify promising biological indicators that could predict the recurrence hazard. The present study employed a CIBERSORT computational method to characterize the immune cell infiltration (ICI) landscape using 549 NMIBC cases from the training cohort. Three ICI phenotypes were characterized and differentially expressed genes (DEGs) were identified and evaluated using Cox regression analysis and protein-protein interaction network construction. A four-gene signature for prognostic prediction in NMIBC patients was ultimately established, which was further evaluated by Kaplan-Meier analysis, revealing a significant recurrence-free survival (RFS) difference. The signature was constructed to stratify NMIBC patients into high- and low-risk groups. For patients in the high-risk group, significantly reduced RFS was observed when compared to patients in the low-risk group. Tissue validation results also showed that CDC20, CPL3A1, PLK1, and FOXM1 were differentially expressed between tumor and normal tissues from NMIBC patients. Results of the receiver operating characteristic curve (ROC) analysis demonstrated that the signature had a significant predictive power for NMIBC recurrence. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the signature manifested close interactions with cell-cycle pathways and tumor environment. In conclusion, this novel cell cycle-related four-gene signature can be used for prognostic prediction in NMIBC.