A novel diagnostic tool for the detection of bladder cancer: Measurement of urinary high mobility group box-1

Abstract

Objective: We aimed to investigate the diagnostic value of urinary High Mobility Group Box-1 (HMGB1) level as a noninvasive tool that can be potentially used for diagnosis and during follow-up in patients with bladder cancer patients.

Method: The study was conducted in a total of 121 participants including 61 patients diagnosed with primary bladder cancer, 30 patients with an acute urinary tract infection and 30 healthy controls. Age, gender and urinary HMGB1 levels of the study groups were evaluated. The association of clinical features (tumor diameter, number of foci, pathological grade, muscle invasion) with urinary HMGB1 levels was investigated in patients with bladder cancer.

Results: All 3 groups showed a normal age and gender distribution with no significant difference among them (P = 0.775 and P = 0.967, respectively). A significant difference was detected in urinary HMGB1 levels among the 3 groups (P < 0.001). When urinary HMGB1 levels were compared between patients with high grade vs. low grade tumors, the mean HMGB1 level was 44.39 pg/ml (12.1-505.2) in patients with low grade tumors and 280 pg/ml (18.7-2685.3) in patients with high grade tumors (P < 0.001). Patients with a greater number of tumor foci had higher HMGB1 levels in comparison to patients with a single tumor focus (P = 0.008). Urinary HMGB1 levels were higher in patients with a tumor diameter of ≥3 cm than in patients with a tumor diameter less than 3 cm (P = 0.001). Patients with muscle-invasive bladder cancer exhibited higher urinary HMGB1 levels compared to patients with non-muscle-invasive bladder cancer (P = 0.033). The cut-off values derived from the ROC analysis were 63.30 pg/ml for distinguishing bladder cancer from urinary tract infection, 30.94 pg/ml for urinary tract infection versus control group and 38.70 pg/ml for bladder cancer vs. control group, respectively. Sensitivity was 59% and specificity was found 77%.

Conclusion: In future controlled studies involving larger patient groups, urinary HMGB1 levels can be used for diagnostic and screening purposes in bladder cancer patients.

Keywords: Bladder cancer; Noninvasive screening test; Tumor marker; Urinary HMGB1; Urine marker.