BackgroundWhile several molecular markers of bladder cancer prognosis have been identified, the limited value of current prognostic markers has created the need for new molecular indicators of bladder cancer outcomes. The aim of this study was to identify genetic signatures associated with disease prognosis in bladder cancer.ResultsWe used 272 primary bladder cancer specimens for microarray analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Microarray gene expression analysis of randomly selected 165 primary bladder cancer specimens as an original cohort was carried out. Risk scores were applied to stratify prognosis-related gene classifiers. Prognosis-related gene classifiers were individually analyzed with tumor invasiveness (non-muscle invasive bladder cancer [NMIBC] and muscle invasive bladder cancer [MIBC]) and prognosis. We validated selected gene classifiers using RT-PCR in the original (165) and independent (107) cohorts. Ninety-seven genes related to disease progression among NMIBC patients were identified by microarray data analysis. Eight genes, a progression-related gene classifier in NMIBC, were selected for RT-PCR. The progression-related gene classifier in patients with NMIBC was closely correlated with progression in both original and independent cohorts. Furthermore, no patient with NMIBC in the good-prognosis signature group experienced cancer progression.ConclusionsWe identified progression-related gene classifier that has strong predictive value for determining disease outcome in NMIBC. This gene classifier could assist in selecting NMIBC patients who might benefit from more aggressive therapeutic intervention or surveillance.

Results strongly suggest that inactivation of RUNX3 by the methylation of its promoter region is a significant risk factor for invasive bladder tumors, tumor progression and cancer specific survival. RUNX3 promoter methylation status could be a promising marker for assessing the prognosis of human bladder tumors.

This study reveals that obesity is associated with metabolic alterations and urinary stone recurrence. Weight control may be considered one of the preventive modalities against recurrent stone formation, especially in first time stone formers.

Bladder cancers comprise heterogeneous cell populations, and numerous factors are likely to be involved in dictating recurrence, progression and patient survival. While several molecular markers that are used to evaluate the development and prognosis of bladder cancer have been studied, the limited value of these established markers has created the need for new molecular indicators of bladder cancer prognosis. Of particular interest is the silencing of tumor-suppressor genes by epigenetic alteration. Recent progress in understanding epigenetic modification and gene silencing has led to new opportunities for the understanding, detection, treatment and prevention of cancer. Moreover, epigenetic silencing of tumor-suppressor genes is interesting from a clinical standpoint, because of the possibility of reversing epigenetic changes and restoring gene function in a cell. This review focuses on the prognostic relevance of epigenetic markers in bladder cancer.

Asymptomatic renal stones can be followed safely but long-term followup is necessary. Periodic followup and early intervention should be recommended in patients with risk factors.