Overexpression of high mobility group box 1 with poor prognosis in patients after radical prostatectomy.
What's known on the subject? and What does the study add? Recent studies have indicated that high mobility group box 1 (HMGB1) is related to the development and progression of human carcinomas. However, further studies were required to confirm the roles played by HMGB1 in clinical prostate cancer treatment. We investigated the relationship between HMGB1 expression and the characteristics of prostate cancer, and also evaluated the significance of HMGB1 as a prognostic factor for biochemical recurrence-free survival 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).


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.
Department of Urology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China. quicktao@gmail.com
Tao
T
Li
Yaping
Y
Gui
Tao
T
Yuan
Guoqiang
G
Liao
Cuidong
C
Bian
Qiquan
Q
Jiang
Shengsong
S
Huang
Bo
B
Liu
Denglong
D
Wu
D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D015153:Blotting, Western; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D024243:HMGB1 Protein / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D024243:HMGB1 Protein; D012334:RNA, Neoplasm