Oncotarget

Clinical Research Papers:

Positive expression of NR6A1/CT150 as a predictor of biochemical recurrence-free survival in prostate cancer patients

Gong Cheng, Shangqian Wang, Xiao Li, Shuang Li, Yang Zheng, Lei Zhang, Meiling Bao, Chao Liang, Zhengkai Huang, Yiyang Liu, Chao Qin, Pengfei Shao, Jie Li, Lixin Hua _, Changjun Yin and Zengjun Wang

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Oncotarget. 2017; 8:64427-64439. https://doi.org/10.18632/oncotarget.11749

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Abstract

Gong Cheng1,*, Shangqian Wang1,*, Xiao Li1,3,*, Shuang Li1,*, Yang Zheng1, Lei Zhang1, Meiling Bao1,2, Chao Liang1, Zhengkai Huang1, Yiyang Liu1, Chao Qin1, Pengfei Shao1, Jie Li1, Lixin Hua1, Changjun Yin1 and Zengjun Wang1

1 Department of Urology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China

2 Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China

3 Department of Urology, the Affiliated Cancer Hospital of Jiangsu Province of Nanjing Medical University, Nanjing, China

* These authors have contributed equally to this work

Correspondence to:

Lixin Hua, email:

Pengfei Shao, email:

Keywords: NR6A1, CT antigens, prostate cancer, gene silencing, EMT

Received: March 29, 2015 Accepted: July 26, 2016 Published: August 31, 2016

Abstract

NR6A1/CT150, as an orphan receptor, is a novel member of the cancer-testis (CT) antigen family. Here, we investigated the expression and function of NR6A1 and its underlying mechanisms in prostate cancer (PCa) patients who underwent radical prostatectomy. A total of 303 cases of prostate cancer after radical prostatectomy were analysed in a tissue microarray (TMA) for NR6A1 immunohistochemistry-based protein expression. Kaplan–Meier/log-rank analysis and Cox regression analysis were used to investigate the relationship between NR6A1 expression and clinicopathological factors in PCa. NR6A1 mRNA expression was examined by reversing transcriptase-polymerase chain reaction (RT-PCR). Knockdown of NR6A1 by small interfering RNA mediated gene silencing and overexpression of NR6A1 through lentivirus were utilized to investigate its potential role in prostate cancer cells. NR6A1 protein expression was 29.7% (90/303) and mRNA expression was 28.1%(9/32) in PCa patients. NR6A1 expression was significantly associated with Gleason score (GS) (P=0.003) and tumor stage (P=0.042). The patients with positive NR6A1 expression have a shorter biochemical recurrence-free survival. NR6A1 predicted biochemical recurrence in univariate (P=0.0159) and multivariate models (P=0.0317). In addition, gene silencing of NR6A1 resulted in G0/G1 phase cell cycle arrest, and decreased metastatic and invasive potential of prostate cancer cells DU145 and PC3. In contrast, overexpression of NR6A1 reduced G0/G1 phase cell cycle arrest, and promoted metastatic and invasive potential of prostate cancer cells 22RV1. And overexpression of NR6A1 significantly promoted tumor growth in vivo. What’s more, down regulation of NR6A1 could reverse epithelial-to-mesenchymal transition (EMT) process in DU145 and PC3 cell lines, and the overexpression could enhance EMT process in 22RV1 cell line. NR6A1 played a prominent role in migration and invasion of PCa cells, and it is indicated that NR6A1 may act as a novel marker for biochemical recurrence after radical prostatectomy.


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