Overexpression of high mobility group box 1 contributes to progressive clinicopathological features and poor prognosis of human bladder urothelial carcinoma

Background: High mobility group box 1 (HMGB1), a versatile protein with intranuclear and extracellular functions, plays an important role in a variety of human cancers. However, the clinical/prognostic significance of HMGB1 expression in human bladder urothelial carcinoma (BUC) remains unclear. The aim of this study was to investigate the HMGB1 expression in human BUC with regard to its clinical and prognostic significance. Patients and methods: HMGB1 mRNA and protein expressions in tumor and paired normal bladder tissues were detected in 20 BUC cases by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. HMGB1 protein expression in 165 primary BUC tissues was evaluated by immunohistochemistry (IHC), and its correlations with clinicopathological characteristics and prognosis were also analyzed. Student's t-test,chi(2) test, Kaplan-Meier plots, and Cox proportional hazard regression model were performed to analyze the data. Results: By using qRT-PCR and Western blot, the upregulated expression of HMGB1 mRNA and protein was detected in BUC, compared with paired normal tissue (P<0.05). By using IHC, high HMGB1 expression was examined in 84 of 165 (51.0%) BUC cases. High HMGB1 expression was significantly correlated with poorer differentiation and higher T and N classification (all P<0.05). Univariate analysis showed that high HMGB1 expression was significantly associated with a shortened patients' overall survival (OS) and disease-free survival (DFS; both P<0.001). In different subgroups of BUC patients, HMGB1 expression was a prognostic factor in patients with different histological grades or T classification (all P<0.05), pN-(both P<0.001) for OS and DFS, and pT1/pN-(P<0.05) for OS. HMGB1 expression, as well as pT and pN status, was an independent prognostic factor for both OS (P=0.001, hazard ratio [HR] =2.973, 95% confidence interval [CI] =1.550-5.704) and DFS (P<0.001, HR =3.019, 95% CI =1.902-4.792) in multivariate analysis. Conclusion: Overexpression of HMGB1 may be a new independent molecular marker for the poor prognosis of patients with BUC.