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Authors Huang CK, Huang ZC, Zhao XK, Wang YH, Zhao HQ, Zhong ZH, Wang L
Received 1 November 2017
Accepted for publication 23 February 2018
Published 12 April 2018 Volume 2018:11 Pages 2111—2120
DOI https://doi.org/10.2147/OTT.S155745
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Justinn Cochran
Peer reviewer comments 2
Editor who approved publication: Dr XuYu Yang
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, χ 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.
Keywords: high mobility group box 1, bladder urothelial carcinoma,
clinicopathology, prognosis