CpG island hypermethylation profile in the serum of men with clinically localized and hormone refractory metastatic prostate cancer
CpG island hypermethylation profile in the serum of men with clinically localized and hormone refractory metastatic prostate cancer
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DOI：
10.1016/j.juro.2007.09.038
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发表时间：
2008-02-01
影响因子：
6.6
通讯作者：
Nelson, William G.
中科院分区：
文献类型：
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作者：
Bastian, Patrick J.;Palapattu, Ganesh S.;Nelson, William G.
目的：我们注意到局限性前列腺癌患者术前血清GSTP1的高甲基化可预测手术治疗后早期前列腺特异性抗原失效。在这项研究中，我们研究了局限性和激素难治性前列腺癌男性血清中几个基因的高甲基化谱。材料和方法：我们检测了192例临床局限性前列腺癌患者和18例激素难治性转移性前列腺癌患者的血清。35份前列腺活检阴性患者的血清样本作为阴性对照。我们评估了特定基因的CpG岛超甲基化状态，包括MDR1、EDNRB、CD44、NEP、PTGS2、RASSF1A、rar - β和ESR1。GSTP1的高甲基化结果包括在先前的研究中。结果：前列腺根治术后无PSA复发的患者中，38.2%的患者MDR1位点CpG岛高甲基化阳性，生化复发的患者中，CpG岛高甲基化阳性的比例为16.1%。在局限性前列腺癌患者的血清中未检测到其余7个基因位点的DNA超甲基化。在转移性前列腺癌患者的血清中，15例（83.3%）检测到CpG岛高甲基化，9例（50%）检测到EDNRB， 7例（38.9%）检测到rar - β， 5例（27.8%）检测到GTSP1, 3例（16.7%）检测到NEP或RASSF1A。在所有样本中均未检测到CD44、PTGS2或ESR位点的CpG岛超甲基化。所有病理正常的病例CpG岛高甲基化均为阴性。结论：在局限性前列腺癌病例中检测到MDR1位点的DNA超甲基化。在晚期疾病的男性中检测到几个基因位点的CpG岛超甲基化。在患有激素难治性疾病的男性中，没有一致观察到单一基因高甲基化。这些结果表明，一组特定基因的CpG岛高甲基化状态可能是激素难治性前列腺癌男性患者的有用生物标志物。
Purpose: We have noted that hypermethylation at GSTP1 in the preoperative serum of men with localized prostate cancer predicts early prostate specific antigen failure following surgical treatment. In this study we investigated the hypermethylation profile of several genes in the serum of men with localized and hormone refractory prostate cancer.Materials and Methods: We assayed the serum of 192 men with clinically localized prostate cancer and 18 with hormone refractory metastatic disease. A total of 35 serum samples from patients with negative prostate biopsy served as a negative control. CpG Island hypermethylation status of certain genes was assessed, including MDR1, EDNRB, CD44, NEP, PTGS2, RASSF1A, RAR-beta and ESR1. The results of hypermethylation at GSTP1 were included from a previous study.Results: CpG island hypermethylation at MDR1 was positive in 38.2% of cases without PSA recurrence and in 16.1% of those with biochemical recurrence after radical prostatectomy. DNA hypermethylation at the remaining 7 gene loci was not detected in the serum of patients with localized prostate cancer. In serum from metastatic prostate cancer cases CpG island hypermethylation was detected at MDR1 in 15 (83.3%), EDNRB in 9 (50%), RAR-beta in 7 (38.9%), GTSP1 in 5 (27.8%) and NEP or RASSF1A in 3 (16.7%). CpG island hypermethylation at CD44, PTGS2 or ESR was not detected in any samples. All histologically normal cases were negative for CpG island hypermethylation.Conclusions: DNA hypermethylation at MDR1 was detected in cases of localized prostate cancer. CpG island hypermethylation at several gene loci was detected in men with advanced disease. No single gene was consistently observed to be hypermethylated in men with hormone refractory disease. These results suggest that the CpG island hypermethylation status of a defined panel of genes may be a useful biomarker in men with hormone refractory prostate cancer.