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Combined overexpression of HIVEP3 and SOX9 predicts unfavorable biochemical recurrence- free survival in patients with prostate cancer

Authors Qin G, He H, Han Z, Liang Y, Yang S, Huang Y, Zhou L, Fu H, Li J, Jiang F, Zhong W

Received 5 October 2013

Accepted for publication 20 November 2013

Published 24 January 2014 Volume 2014:7 Pages 137—146

DOI https://doi.org/10.2147/OTT.S55432

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2


Guo-qiang Qin,1,2,* Hui-chan He,2,* Zhao-dong Han,2,* Yu-xiang Liang,2 Sheng-bang Yang,2 Ya-qiang Huang,2 Liang Zhou,2 Hao Fu,2 Jie-xian Li,1,2 Fu-neng Jiang,2 Wei-de Zhong2–4

1Central Hospital of Panyu District, Guangzhou, People's Republic of China; 2Department 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; 3Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, People's Republic of China; 4Urology Key Laboratory of Guangdong Province, Guangzhou Medical University, Guangzhou, People's Republic of China

*These authors contributed equally to this article

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.
Conclusion: 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.

Keywords: prostate cancer, HIVEP3, SOX9, clinicopathological feature, biochemical recurrence-free survival

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