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Feasibility of assessment of promoter methylation of the CD44 gene in serum of prostate cancer patients

机译：评估前列腺癌患者血清中CD44基因启动子甲基化的可行性

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Background and Purpose: CD44 is an important metastasis-suppressor gene in prostate cancer. Downregulation of the CD44 gene is attributed to transcription repression by methylation of CpG islands in the promoter region. The feasibility of CD44 promoter methylation measurement as a diagnostic tool was assessed in the serum of patients with cancer of the prostate (CAP). Materials and Methods: Seven serum samples of patients with CAP were investigated for CD44 promoter methylation by methylation-specific PCR. Three patients had proven metastatic disease, and four were free of metastases. Tissues from a variety of normal epithelia were assessed as well. Results: Methylation of the CD44 promoter was readily detectable in all serum samples, although no distinction could be made between patients with and those without metastatic disease on the basis of the signal intensity of methylation-specific PCR products. Remarkably, tissue specimens from different normal epithelia, especially those of the colon and rectum, repeatedly showed aberrant methylation of the promoter region of CD44. Conclusions: In the serum of CAP patients, assessment of the methylation status of CpG islands in the promoter region of the CD44 gene is feasible using methylation-specific PCR. However, because of physiologic promoter methylation in normal tissues, including the colorectal mucosa, assessment of methylation of tumor-derived DNA in the serum of cancer patients lacks tissue specificity and seems not to be applicable in clinical settings.
机译：背景与目的：CD44是前列腺癌中重要的转移抑制基因。 CD44基因的下调归因于启动子区域CpG岛甲基化的转录抑制。在患有前列腺癌（CAP）的患者的血清中评估了CD44启动子甲基化测量作为诊断工具的可行性。材料和方法：通过甲基化特异性PCR对7例CAP患者的血清样本进行CD44启动子甲基化研究。三名患者已证明具有转移性疾病，四名患者无转移。还评估了来自各种正常上皮的组织。结果：尽管根据甲基化特异性PCR产物的信号强度无法区分有转移性疾病的患者和没有转移性疾病的患者，但在所有血清样品中都容易检测到CD44启动子的甲基化。值得注意的是，来自不同正常上皮的组织标本，特别是结肠和直肠组织的标本，反复显示CD44启动子区的甲基化异常。结论：在CAP患者的血清中，使用甲基化特异性PCR可以评估CD44基因启动子区域CpG岛的甲基化状态。但是，由于包括结直肠粘膜在内的正常组织中的生理启动子甲基化，对癌症患者血清中肿瘤来源的DNA的甲基化的评估缺乏组织特异性，并且似乎不适用于临床环境。

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