Overexpression of high mobility group box 1 with poor prognosis in patients after radical prostatectomy

OBJECTIVE To investigate high mobility group box 1 (HMGB1) expression in human prostate cancer (PC) cell lines and its prognostic significance after radical prostatectomy (RP). PATIENTS AND METHODS Quantitative reverse-transcription polymerase chain reaction and western blotting were used to detect HMGB1 mRNA and protein expression in PC cell lines. Immunohistochemistry coupled with the tissue microarray technique was performed to evaluate HMGB1 protein expression in 168 primary prostatectomy tissue samples. Clinicopathological features were compared between positive and negative HMGB1 protein expression groups. Kaplan-Meier and multivariate Cox analyses were applied to determine the prognostic value of HMGB1 protein expression on biochemical recurrence (BCR) for patients with PC who were undergoing RP. RESULTS There were three PC cells (DU145, PC-3 and LNCaP) with overexpression of HMGB1 mRNA and protein compared to the non-transformed immortalized prostate cell RWPE-1. A total of 60.1% (101/168) of the PC samples appeared to have positive protein expression of HMGB1. HMGB1 protein expression was correlated with some clinicopathological parameters, such as pathological stage (pT) (P = 0.011), Gleason score, preoperative prostate-specific antigen concentration and BCR (P < 0.001, respectively). Positive HMGB1 immunostaining in patients with PC who were undergoing RP was significantly associated with poor median BCR-free survival (23.1 months vs 15.6 months) (P < 0.001). Multivariate analysis indicated that HMGB1 protein expression was an independent prognostic factor for BCR-free survival after RP (hazard ratio = 2.348, 95% confidence interval = 1.373-6.361, P = 0.001). CONCLUSIONS Up-regulation of HMGB1 mRNA and protein concentrations was confirmed in PC cells. HMGB1 expression may contribute to the malignant progression of PC. HMGB1 presents as a novel prognostic factor for BCR after RP.