DJ-1 Expression Might Serve as a Biologic Marker in Patients with Bladder Cancer

SIMPLE SUMMARY: Although serum DJ-1 has been evaluated in some types of cancer, it has not been analyzed in detail in bladder cancer (BC). Furthermore, DJ-1 expression patterns in BC and their clinicopathologic significance and relationship with prognosis are unclear. In the present study, we evaluated serum DJ-1 levels in BC and the localization of DJ-1 expression in BC tissues. Our research showed that serum DJ-1 was significantly higher in 172 patients with BC who underwent the transurethral resection of bladder tumors (TURBT) than in those with urolithiasis or in healthy participants. Immunohistochemically, a DJ-1 cytoplasm-positive (Cy+) and nucleus-negative (N−) pattern in 92 archived radical cystectomy BC specimens was associated with a significantly increased risk for lower overall, recurrence-free and cancer-specific survival. Our findings suggest that DJ-1 might be a new biomarker for diagnosing BC and predicting biologically aggressive cancers so as to determine the appropriate treatment modality after radical cystectomy. ABSTRACT: The overexpression of DJ-1 protein and its secretion into the bloodstream has been reported in various neoplasms. However, serum levels and the subcellular localization of DJ-1 have not been analyzed in detail in bladder cancer (BC). Our comprehensive analysis of these variables started with the measurement of DJ-1 in serum from 172 patients with BC, 20 patients with urolithiasis and 100 healthy participants. Next, an immunohistochemical study of DJ-1 expression and localization was conducted in 92 patients with BC, and associations with clinicopathologic factors and patient outcomes were evaluated. Serum DJ-1 was significantly higher in patients with BC than in those with urolithiasis or in healthy participants. Immunohistochemically, a cytoplasm-positive (Cy+) and nucleus-negative (N−) DJ-1 pattern was associated with age and pathologic stage. Log-rank tests indicated that the Cy+, N− pattern was significantly associated with overall survival (OS), recurrence-free survival (RFS), and cancer specific survival (CSS). In addition, the Cy+, N− pattern was an independent prognostic factor in the multivariate analysis adjusted for the effects of the clinicopathologic outcomes. The investigation of DJ-1 expression might help physicians to make decisions regarding further follow-up and additional treatments.