前列腺癌组织中DNMT1的表达与GSTP1、APC甲基化状态的关系及临床意义

Correlation of DNMT1 expression with GSTP1 and APC methylation and its clinical significance

目的探讨前列腺癌组织中DNA甲基转移酶1(DNA methyltransferase 1,DNMT1)的表达与谷胱甘肽S转移酶P1(glutathione S transferase P1,GSTP1)、结肠腺瘤性息肉病(adenomatous polyposis coli,APC)甲基化状态的关系及临床意义。方法采用RT-PCR的方法检测56例前列腺癌(prostate cancer,PCa)组织和10例前列腺增生(benign prostatichyperplasia,BPH)组织中DNMT1和GSTP1、APC的mRNA表达,采用甲基化特异性PCR(MS-PCR)的方法检测GSTP1、APC的启动子区CpG岛甲基化状态。结果大多数PCa组织中DNMT1 mRNA高表达(在低分化癌中阳性率为90.0%),而GSTP1和APC低表达(在低分化癌中阳性率分别为23.3%和33.3%),BPH组织中DNMT1 mRNA低表达(40.0%),而GSTP1和APC高表达(分别为90.0%和80.0%),低分化癌与BPH相比,差异有统计学意义(P<0.05);大多数PCa组织中GSTP1、APC启动子区CpG岛呈高甲基化状态(在低分化癌中阳性率分别为83.3%和73.3%),而BPH组织中呈低甲基化(阳性率分别为10.0%和20.0%),低分化癌与BPH相比,差异有统计学意义(P<0.05)。结论 PCa组织中GSTP1、APC失活的机制可能与DNMT1的高表达导致其启动子区CpG岛异常高甲基化有关。

Objective To investigate the correlation of expression of DNA methyltransferase 1 （ DNMT1 ） and the methylation status of glutathione S transferase PI （ GSTPI ） and adenomatous polyposis coli （APC） promoter CpG island in prostate cancer and its clinical significance. Methods RT-PCR method was used to detect the expression of DNMT1, GSTP1, and APC in 56 cases of prostate cancer and 10 cases of benign prostatic hyperplasia. Mutagenivcally separated-PCR （MS-PCR） was used to detect the methylation status of CpG island of promoter of GSTP1 and APC. Results DNMT1 mRNA was highly expressed in most of the prostate cancer tissue （ the positive rate in the poorly-differentiated cancer tissues was 90.0% ）, but mildly expressed in benign prostatic hyperplasia （ the positive rate was 40.0% ）. GSTP1 and APC mRNA was slightly expressed in most of the prostate cancer tissue （the positive rate of poor-differentiation was 23.3% and 33.3% respectively, P 〈 0.05 ）, but strongly expressed in most benign prostatic hyperplasia tissue （ the positive rate was 90.0% and 80.0% respectively）. GSTPI and APC were in hypermethylated status in most prostate cancer tissues （the positive rate of poor-differentiation was 83.3% and 73.3% respectively）, but in hypomethylated status （ of demethylation） in benign prostatic hyperplasia （the positive rate was 10.0% and 20.0% respectively, P 〈 0.05）. Conclusion Silence of GSTP and APC in prostate cancer may be related with hyiSermethylation of DNMT1 promoter CpG island due to its high expression.