前列腺癌患者外周血中前列腺癌抗原3基因和前列腺特异性抗原基因联合检测的意义

摘要

Objective To evaluate the application value of combined detection of PCA3 and PSA mRNA in peripheral blood of patients with prostate cancer(PCa) for evaluation of mien)metastasis. Methods PCA3 and PSA mRNA were detected by duplex real time quantitative RT-PCR in a total of 49 PCa and 71 benign protatic hyperplasia (BPH) patients' peripheral blood. The diagnostic value was analyzed by receiver operative characteristic(ROC) curve. Results The levels of PCA3 mRNA in PCa patients were significantly higher than those in BPH patients [2 362( <30-7 421 ) copies/ml vs <30 copies/M, Z = -6. 66, P < 0. 01 ], and the same to PSA mRNA [3 425 ( 908-36 639 ) copies/ml vs < 200 copies/ml, Z = - 6. 40, P<0. 01 ]. The positive rate of PCA3 and PSA mRNA in peripheral blood was positively correlated with clinical stage[clinical stage B: 30.0% (3/10), C: 60.0% (9/15) and 86.7% (13/15), D: 91.7% (22/24) and 91.7% (22/24) ,Chi-square = 13. 534 and 16. 541, P <0. 01, respectively]. Meanwhile, the positive rate of PCA3 mRNA and PSA mRNA was also increased with the increase of Gleason score[ Gleason score of 2 to 4 : 20.0% (1/5) and 40. 0% (2/5) ;5 to 7 : 66.7% (12/18) and 72. 2% ( 13/18 ) ;8 to 10 : 84. 6% (22/26) and 92.3% ( 24/26 ) ;Chi-square = 8. 895 and 8. 015, P < 0. 05, respectively ]. ROC analysis showed that the sensitivities for PCA3 and PSA mRNA were 69. 4% (34/49) and 81.7% (40/49) and the specificities was 90. 1% (64/71) and 77.5% (55/71), respectively, when the cut-off value was 846 copies/ml for PCA3 mRNA and 280 copies/ml for PSA mRNA. Meanwhile, the sensitivity can reach to 85.7% (42/49) when the detection of PCA3 and PSA mRNA were combined. However, the specificity was decreased to 76. 1% (54/71). For the diagnosis of PCa micrometastasis, the sensitivity and specificity for PCA3 mRNA was 90.9% (20/22) and 84.7% (11/13), respectively. Conclusions PCA3 and PSA mRNA in peripheral blood are useful markers for PCa diagnosis. Simultaneous detection for PCA3 and PSA mRNA is more helpful for PCa diagnosis. Meanwhile, detection of PCA3 mRNA is a useful marker for diagnosing PCa micrometastasis.%目的 评价外周血前列腺痛抗原3基因(prostate cancer antigen 3,PCA3 mRNA)和前列腺特异性抗原基因(prostate specific antigen,PSA mRNA)联合检测对前列腺癌(PCa)及对其微转移诊断的价值.方法 用双重荧光实时定量逆转录(dFQ-RT)-PCR对49例PCa和71例前列腺增生(BPH)患者外周血PCA3 mRNA和PSA mRNA进行定量检测,通过受试者工作特征(ROC)曲线评价其在PCa诊断和微转移监测中的价值.结果 PCa组外周血PCA3 mRNA含量明显高于BPH组[2 362(<3-7 421)拷贝/ml比<30拷贝/ml,Z=-6.66,P<0.01],而PSA mRNA含量也明显高于BPH组[3 425(908～36 639)拷贝/ml比<200拷贝/ml,Z=-6.40,P<0.01];PCa组外周血PCA3mRNA和PSA mRNA的阳性率随临床分期增高而增加[B期:均为30.0%(3/10),C期:60.0%(9/15)和86.7%(13/15),D期:91.7%(22/24)和91.7%(22/24);χ2分别为13.534和16.451,P均<0.01],同时也随Gleason评分增高而增加[2～4分:20.0%(1/5)和40.0%(2/5);5～7分:66.7%(12/18)和72.2%(13/18);8～10分:84.6%(22/26)和92.3%(24/26);χ2分别为8.895和8.015,P均<0.05];ROC曲线显示,当PCA3 mRNA和PSA mRNA临界值分别为846拷贝/ml和280拷贝/ml时,诊断PCa敏感度分别为69.4%(34/49)和81.7%(40/49),特异度分别为90.1%(64/71)和77.5%(55/71);而联合检测时其敏感度可增至85.7%(42/49),但特异度下降为76.1%(54/71).PCA3 mRNA诊断PCa微转移的敏感度和特异度分别为90.9%(20/22)和84.7%(11/13).结论 外周血PCA3 mRNA和PSA mRNA检测是PCa诊断的良好指标,而联合检测可弥补PCA3 mRNA敏感度低和PSA mRNA特异度低的不足,而更有利于PCa诊断;PCA3 mRNA可能为PCa微转移诊断的良好指标.