Prognostic value of promoter hypermethylation of Retinoic Acid Receptor Beta (RARB) and CDKN2 (p16/MTS1) in prostate cancer

Prognostic value of promoter hypermethylation of Retinoic Acid Receptor Beta (RARB) and CDKN2 (p16/MTS1) in prostate cancer
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DOI:
10.1007/s11670-011-0306-x
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发表时间:
2011-12-01
影响因子:
5.1
通讯作者:
Fadavi, P.
Fadavi, P.
中科院分区:
医学3区
文献类型:
--
作者:
Ameri, A.;Alidoosti, A.;Fadavi, P.

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前列腺癌的分子机制知之甚少。为探讨前列腺增生症(BPH)和前列腺癌患者中维甲酸受体β(RARB)和p16基因启动子高甲基化的发生率及其预后价值,采用病例对照研究方法,将63例BPH和前列腺癌患者分为3组:21例BPH为对照组,21例前列腺癌及预后良好因素根据前列腺特异性抗原(PSA)、Gleason评分和分期确定为预后良好组,21例伴有前列腺癌和预后不良特征的患者为预后不良组。采用甲基化特异性PCR(methylation specific PCR,MSPCR)检测前列腺组织中RARB和p16基因启动子甲基化,结果显示:预后良好组RARB甲基化阳性率为33.3%,预后不良组为71.4%,均显著高于对照组(P < 0.0001)。p16基因启动子甲基化阳性率分别为19.0%和47.6%。预后不良组RARB和p16基因启动子甲基化水平显著高于预后良好组(P =0.02,P < 0.0001),提示RARB和p16基因启动子甲基化可能是预测前列腺癌预后的指标。
The molecular mechanism of prostate cancer is poorly understood. The aim of the study was to investigate the prevalence and prognostic value of promoter hypermethylation of retinoic acid receptor beta (RARB) and p16 among benign prostatic hyperplasia (BPH) and prostate cancer patients.In this case-control study, 63 patients were included in three groups; 21 with BPH as the control group, 21 with prostate cancer and good prognostic factors (based on prostate-specific antigen, Gleason score and stage) as good prognosis group, and 21 with prostate cancer and poor prognostic features as poor prognosis group. The prostate biopsy specimen of each individual was examined for hypermethylation of RARB and p16 promoters by methylation specific PCR (MSPCR).Seven (33.3%) patients with good prognosis and 15 (71.4%) patients with poor prognosis were positive for RARB methylation, which were significantly higher than controls (P < 0.0001). p16 promoter methylation was shown in 19.0% and 47.6% patients with good and poor prognosis, respectively. The RARB and p16 promoter methylation in the poor prognosis group was significantly higher than that in the good prognosis group (P =0.02 for RARB and P < 0.0001 for p16).Hypermethylation of RARB and p16 promoters may predict prognosis in prostate cancer.