DNA甲基转移酶1（DNMT1）、谷胱甘肽S-转移酶P1（GSTP1）和腺瘤性息肉病基因（APC）的表达与GSTP1和APC的甲基化状态之间的相关性及其在前列腺癌中的临床意义。
Correlation between the expression of DNMT1, and GSTP1 and APC, and the methylation status of GSTP1 and APC in association with their clinical significance in prostate cancer.
作者信息
Zhang Weijie, Jiao Hongliang, Zhang Xudong, Zhao Ruihua, Wang Feng, He Wei, Zong Hong, Fan Qingxia, Wang Liuxing
机构信息
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
出版信息
Mol Med Rep. 2015 Jul;12(1):141-6. doi: 10.3892/mmr.2015.3402. Epub 2015 Mar 3.
The aim of the present study was to investigate the correlation between the expression of DNA (cytosine‑5)‑methyltransferase 1 (DNMT1), glutathione S‑transferase‑P1 (GSTP1) and adenomatous polyposis coli (APC), and the methylation status of GSTP1 and APC in prostate cancer (PCa) and benign prostatic hyperplasia (BPH), and to examine its clinical significance. Immunohistochemistry and reverse transcription‑polymerase chain reaction (RT‑PCR) was used to detect the expression of DNMT1, GSTP1 and APC in 56 samples of PCa tissue and 10 samples of BPH tissue. Methylation‑specific‑PCR was used to detect the methylation status of the CpG island promoters of GSTP1 and APC. The positive rate of expression of DNMT1 in poorly‑differentiated PCa, moderately‑differentiated PCa, well‑differentiated PCa and BPH was 86.7%, 70.6%, 55.6% and 30.0%, respectively (P<0.05); for GSTP1, the positive rate was 13.3%, 29.4%, 44.4% and 90.0%, respectively (P<0.05); and for APC, the positive rate was 23.3%, 47.6%, 55.6% and 70.0%, respectively (P<0.05). The correlation coefficient for the association between the expression of DNMT1 and GSTP1 was ‑0.891 (P<0.05). Between the expression of DNMT1 and APC, the correlation coefficient was ‑0.721 (P<0.05). GSTP1 and APC were hypermethylated in the majority of PCa tissue samples. The positive rate of methylation of these genes in poorly‑differentiated PCa was 83.3% and 73.3%, respectively. By contrast, hypomethylation (or demethylation) was observed in BPH samples, in which the positive rate of methylation was 10.0% and 20.0%, respectively (P<0.05). The increased expression of DNMT1, and the reduced expression of GSTP1 and APC have an important role in the development of PCa. Due to the high expression of DNMT1 mRNA, it is likely that the hypermethylation of CpG islands contributed to the silencing of GSTP1 and APC in PCa tissues.
本研究旨在探讨DNA（胞嘧啶-5）-甲基转移酶1（DNMT1）、谷胱甘肽S-转移酶-P1（GSTP1）和腺瘤性息肉病基因（APC）的表达与前列腺癌（PCa）和良性前列腺增生（BPH）中GSTP1和APC的甲基化状态之间的相关性，并探讨其临床意义。采用免疫组织化学和逆转录-聚合酶链反应（RT-PCR）检测56例PCa组织样本和10例BPH组织样本中DNMT1、GSTP1和APC的表达。采用甲基化特异性PCR检测GSTP1和APC的CpG岛启动子的甲基化状态。DNMT1在低分化PCa、中分化PCa、高分化PCa和BPH中的阳性表达率分别为86.7%、70.6%、55.6%和30.0%（P<0.05）；GSTP1的阳性表达率分别为13.3%、29.4%、44.4%和90.0%（P<0.05）；APC的阳性表达率分别为23.3%、47.6%、55.6%和70.0%（P<0.05）。DNMT1与GSTP1表达之间的相关系数为-0.891（P<0.05）。DNMT1与APC表达之间的相关系数为-0.721（P<0.05）。大多数PCa组织样本中GSTP1和APC呈高甲基化。这些基因在低分化PCa中的甲基化阳性率分别为83.3%和73.3%。相比之下，BPH样本中观察到低甲基化（或去甲基化），其甲基化阳性率分别为10.0%和20.0%（P<0.05）。DNMT1表达增加以及GSTP1和APC表达降低在PCa的发生发展中起重要作用。由于DNMT1 mRNA的高表达，PCa组织中CpG岛的高甲基化可能导致GSTP1和APC沉默。
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