Prognostic factors of non-muscle invasive bladder cancer: a study based on next-generation sequencing

Cancer Cell Int. 2021 Jan 6;21(1):23. doi: 10.1186/s12935-020-01731-9.


Objective: To investigate the genetic prognostic factors for the recurrence of non-muscle invasive bladder cancer.

Materials and methods: The patients underwent transurethral resection of bladder tumor and received bacillus Calmette-Guérin (BCG) or epirubicin. Next-generation sequencing was performed and alterations of genes, pathways, and tumor mutation burden were recorded. Associations between these clinicopathological and genetic variants were estimated, and prognostic factor identified.

Results: A total of 58 cases were included in our study, and 46 patients underwent treatment with BCG. FGFR3 was the most frequently altered gene (48%), and more commonly detected in intermediate-risk patients. Univariate Cox analysis demonstrated that 10 genes were significantly correlated with BCG failure, while NEB, FGFR1 and SDHC were independent recurrence predictors. Besides, epigenetic-related gene pathway mutations were negatively correlated with recurrence (hazard ratio: 0.198, P = 0.023). DNA damage response and repair gene alterations were positively correlated with tumor burden, while altered TP53 was most frequent among these genes and significant correlated with high tumor burden.

Conclusion: BCG instillation significantly reduced the rate of recurrence compared with epirubicin in this population. Potential biomarkers and therapeutic targets were found with the help of next-generation sequencing; correlations between DDR genes alterations and high tumor mutation burden were also demonstrated.

Keywords: Bacillus Calmette–Guérin; Bladder cancer; DNA damage response and repair; Next-generation sequencing; Predictive model.