在前列腺癌患者的血液和尿液样本中检测α-甲基酰基辅酶A消旋酶转录本。
Detection of alpha-methylacyl-coenzyme-A racemase transcripts in blood and urine samples of prostate cancer patients.
作者信息
Zehentner Barbara K, Secrist Heather, Zhang XinQun, Hayes Dawn C, Ostenson Richard, Goodman Gary, Xu Jiangchun, Kiviat Mark, Kiviat Nancy, Persing David H, Houghton Raymond L
机构信息
HematoLogics Inc., Seattle, Washington 98109, USA.
出版信息
Mol Diagn Ther. 2006;10(6):397-403. doi: 10.1007/BF03256217.
BACKGROUND
Alpha-methylacyl-coenzyme-A racemase (AMACR) has been shown to be a highly specific marker for prostate cancer cells, even in the earliest stages of malignant progression. It is expressed at much higher levels than prostate-specific antigen (PSA) in malignant tissues, and is not expressed at appreciable levels in normal prostatic epithelium. In this study, we demonstrate the quantitative detection of AMACR transcripts in peripheral blood of prostate cancer patients using real-time RT-PCR. In addition, we have undertaken a pilot study to demonstrate the potential application of this technique for the detection of prostate tumor cells in urine samples from patients with prostate cancer.
METHODS
A real-time RT-PCR assay was developed for detection of the expression of AMACR in prostate cancer patients. Blood samples from 163 patients were tested at various stages of disease progression, with or without therapy. Blood specimens from patients with benign prostate disorders and other types of cancer were also evaluated.
RESULTS
In 28 of 58 samples from patients with known metastatic disease who were undergoing treatment, an AMACR expression signal above the cut-off value was detected, consistent with the presence of circulating tumor cells. In 39 of 88 patients with presumptive organ-confined disease, there was evidence of low levels of circulating tumor cells. Comparison of AMACR RT-PCR with known serum PSA values indicated that a combination of these parameters significantly increased the sensitivity for detection of progressive disease. In a pilot study analyzing urine samples from seven prostate cancer patients, elevated AMACR expression levels were detected in the urine sediments of four of six stage-T1 prostate cancer patients and in the one patient with stage-T2 prostate cancer.
CONCLUSION
The data presented in this study indicates that AMACR real-time RT-PCR may aid in the detection and staging of prostate cancer.
背景
α-甲基酰基辅酶A消旋酶（AMACR）已被证明是前列腺癌细胞的一种高度特异性标志物，即使在恶性进展的最早阶段也是如此。它在恶性组织中的表达水平远高于前列腺特异性抗原（PSA），而在正常前列腺上皮中无明显表达。在本研究中，我们使用实时逆转录聚合酶链反应（RT-PCR）证明了对前列腺癌患者外周血中AMACR转录本的定量检测。此外，我们进行了一项初步研究，以证明该技术在检测前列腺癌患者尿液样本中前列腺肿瘤细胞方面的潜在应用。
方法
开发了一种实时RT-PCR检测方法，用于检测前列腺癌患者中AMACR的表达。对163例患者在疾病进展的不同阶段（无论是否接受治疗）的血样进行了检测。还评估了患有良性前列腺疾病和其他类型癌症患者的血样。
结果
在接受治疗的58例已知转移性疾病患者的样本中，有28例检测到AMACR表达信号高于临界值，这与循环肿瘤细胞的存在一致。在88例推定器官局限性疾病患者中，有39例有低水平循环肿瘤细胞的证据。AMACR RT-PCR与已知血清PSA值的比较表明，这些参数的组合显著提高了对进展性疾病检测的敏感性。在一项对7例前列腺癌患者尿液样本的初步研究中，在6例T1期前列腺癌患者中的4例以及1例T2期前列腺癌患者的尿液沉淀物中检测到AMACR表达水平升高。
结论
本研究提供的数据表明，AMACR实时RT-PCR可能有助于前列腺癌的检测和分期。
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