Combined overexpression of HIVEP3 and SOX9 predicts unfavorable biochemical recurrence-free survival in patients with prostate cancer.
BACKGROUND
To clarify the involvement of HIVEP3 and SOX9 coexpression in prostate cancer (PCa).


METHODS
A small interfering RNA was used to knockdown SOX9 expression in a PCa cell line and to analyze the effects of SOX9 inhibition on the expression of HIVEP3 in vitro. Then, HIVEP3 and SOX9 expression patterns in the human PCa tissues were detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry.


RESULTS
We found that the downregulation of SOX9 could inhibit the expression of HIVEP3 in the PCa cells in vitro. In addition, both HIVEP3 and SOX9 messenger RNA expression levels in the PCa tissues were significantly higher than those in the noncancerous prostate tissues (P=0.006 and P<0.001, respectively). Moreover, the immunohistochemical staining scores of HIVEP3 in the PCa tissues with PSA failure were significantly higher than those without (P=0.042); the increased SOX9 protein expression was more frequently found in the PCa tissues with a high Gleason score (P=0.045) and a high clinical stage (P=0.012). The tumors showing the HIVEP3-high/SOX9-high expression more frequently had PSA failure (P=0.024). When the patients with an HIVEP3 overexpression combined with the SOX9 overexpression, this group had a worse biochemical recurrence-free survival (P<0.001). Furthermore, the multivariate analysis showed that the HIVEP3/SOX9 coexpression was an independent predictor of an unfavorable biochemical recurrence-free survival.


CONCLUSIONS
Our data offer the convincing evidence for the first time that a combined analysis of HIVEP3 and SOX9 may help to predict the tumor progression and prognosis of PCa patients. In particular, the overexpression of HIVEP3 in PCa might partly explain the poor prognosis of patients with an upregulation of SOX9.
Central Hospital of Panyu District, Guangzhou, People's Republic of China ; Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Guo-Qiang
GQ
Qin
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Hui-Chan
HC
He
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Zhao-Dong
ZD
Han
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Yu-Xiang
YX
Liang
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Sheng-Bang
SB
Yang
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Ya-Qiang
YQ
Huang
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Liang
L
Zhou
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Hao
H
Fu
Central Hospital of Panyu District, Guangzhou, People's Republic of China ; Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Jie-Xian
JX
Li
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Fu-Neng
FN
Jiang
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China ; Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, People's Republic of China ; Urology Key Laboratory of Guangdong Province, Guangzhou Medical University, Guangzhou, People's Republic of China.
Wei-de
WD
Zhong
HIVEP3; SOX9; biochemical recurrence-free survival; clinicopathological feature; prostate cancer