Zhou Wu, Tao Zhihua, Wang Zhongyong, Hu Wangqiang, Shen Mo, Zhou Lianlian, Wen Zhiliang, Yu Zhixian, Wu Xiuling, Huang Kate, Hu Yuanping, Lin Xiangyang
Department of Medical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, PR China.
Department of Medical Laboratory, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang, PR China.
Exp Mol Pathol. 2014 Dec;97(3):550-3. doi: 10.1016/j.yexmp.2014.11.005. Epub 2014 Nov 11.
Long noncoding RNA prostate cancer gene antigen 3 (PCA3) is one of the most prostate cancer-specific genes at present. Consequently, the prostate-specific expression and the sharp up-regulation of PCA3 RNA in prostate cancer suggest a unique transcriptional regulation, which possibly can be attributed to promoter polymorphism. In this study, we investigated a short tandem repeat (STR) polymorphism of TAAA in the promoter region of PCA3 gene found in our previous study in prostate cancer (PCa) patients and benign prostatic hypertrophy (BPH) patients, aiming to evaluate the association between the STR and increased risk for PCa.
120 PCa cases and 120 benign prostatic hypertrophy (BPH) cases were identified among participants. The region encompassing the TAAA repeat was amplified with a specific primer set we designed and screened by PCR-based cloning and sequencing in paired peripheral blood leukocytes and prostate tissues. Genotype-specific risks were estimated as odds ratios (ORs) associated with 95% confidence intervals (CIs) and adjusted for age by means of unconditional logistic regression.
5 PCA3 TAAA STR polymorphisms and 8 genotypes were found in both peripheral blood leukocytes and prostate tissues, the carriers with more TAAA repeats were associated with increased risk for PCa than individuals having less TAAA repeats. Interestingly, 18 (15.0%) of 120 PCa patients had more (TAAA)n repeats in prostate tissues than that in peripheral blood leukocytes, and 3 (2.5%) of 120 had less (TAAA)n repeats in prostate tissues.
The results of this study suggest that short tandem repeat polymorphism of TAAA in the promoter region of PCA3 gene is a risk-increasing factor for prostate cancer in the Chinese population. In addition to the hereditary factor, the insertion mutation of (TAAA)n in a local tissue maybe another mechanism of the onset of PCa.
长链非编码RNA前列腺癌基因抗原3（PCA3）是目前最具前列腺癌特异性的基因之一。因此，PCA3 RNA在前列腺癌中的前列腺特异性表达及急剧上调提示了一种独特的转录调控，这可能归因于启动子多态性。在本研究中，我们调查了在先前对前列腺癌（PCa）患者和良性前列腺增生（BPH）患者的研究中发现的PCA3基因启动子区域TAAA的短串联重复序列（STR）多态性，旨在评估该STR与PCa风险增加之间的关联。
在参与者中确定了120例PCa病例和120例良性前列腺增生（BPH）病例。使用我们设计的特异性引物对扩增包含TAAA重复序列的区域，并通过基于PCR的克隆和测序在配对的外周血白细胞和前列腺组织中进行筛选。将基因型特异性风险估计为与95%置信区间（CIs）相关的比值比（ORs），并通过无条件逻辑回归对年龄进行调整。
在外周血白细胞和前列腺组织中均发现了5种PCA3 TAAA STR多态性和8种基因型，与TAAA重复序列较少的个体相比，TAAA重复序列较多的携带者患PCa的风险增加。有趣的是，120例PCa患者中有18例（15.0%）前列腺组织中的（TAAA）n重复序列比外周血白细胞中的多，120例中有3例（2.5%）前列腺组织中的（TAAA）n重复序列较少。
本研究结果表明，PCA3基因启动子区域TAAA的短串联重复序列多态性是中国人群前列腺癌的一个风险增加因素。除遗传因素外，局部组织中（TAAA）n的插入突变可能是PCa发病的另一种机制。
