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检测尿沉渣中的TMPRSS2-ERG融合转录本和前列腺癌抗原3可能会改善前列腺癌的诊断。

Detection of TMPRSS2-ERG fusion transcripts and prostate cancer antigen 3 in urinary sediments may improve diagnosis of prostate cancer.

作者信息

Hessels Daphne, Smit Frank P, Verhaegh Gerald W, Witjes J Alfred, Cornel Erik B, Schalken Jack A

机构信息

Experimental Urology, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.

出版信息

Clin Cancer Res. 2007 Sep 1;13(17):5103-8. doi: 10.1158/1078-0432.CCR-07-0700.

Abstract

PURPOSE

Early detection of prostate cancer can increase the curative success rate for prostate cancer. We studied the diagnostic usefulness of TMPRSS2-ERG fusion transcripts as well as the combination of prostate cancer antigen 3 (PCA3) RNA and TMPRSS2-ERG fusion transcripts in urinary sediments after digital rectal examination (DRE).

EXPERIMENTAL DESIGN

A total of 78 men with prostate cancer-positive biopsies and 30 men with prostate cancer-negative biopsies were included in this study. After DRE, the first voided urine was collected, and urinary sediments were obtained. We used semiquantitative reverse transcription-PCR (RT-PCR) analysis followed by Southern blot hybridization with a radiolabeled probe for the detection TMPRSS2-ERG fusion transcripts in these urinary sediments. A quantitative RT-PCR assay for PCA3 was used to determine the PCA3 score in the same sediments.

RESULTS

TMPRSS2-ERG fusion transcripts can be detected in the urine after DRE with a sensitivity of 37%. In this cohort of patients, the PCA3-based assay had a sensitivity of 62%. When both markers were combined, the sensitivity increased to 73%. Especially in the cohort of men with persistently elevated serum prostate-specific antigen levels and history of negative biopsies, the high positive predictive value of 94% of TMPRSS2-ERG fusion transcripts could give a better indication which patients require repeat biopsies.

CONCLUSION

In this report, we used for the first time the combination of the prostate cancer-specific biomarkers TMPRSS2-ERG and PCA3, which significantly improves the sensitivity for prostate cancer diagnosis.

摘要

目的

早期发现前列腺癌可提高前列腺癌的治愈成功率。我们研究了跨膜蛋白酶丝氨酸2-ETS相关基因(TMPRSS2-ERG)融合转录本以及前列腺癌抗原3(PCA3)RNA与TMPRSS2-ERG融合转录本联合检测在直肠指检(DRE)后尿沉渣中对前列腺癌的诊断价值。

实验设计

本研究共纳入78例前列腺活检阳性的男性和30例前列腺活检阴性的男性。DRE后,收集首次晨尿并获取尿沉渣。我们采用半定量逆转录聚合酶链反应(RT-PCR)分析,随后用放射性标记探针进行Southern印迹杂交,以检测这些尿沉渣中的TMPRSS2-ERG融合转录本。采用PCA3定量RT-PCR检测法测定同一沉渣中的PCA3评分。

结果

DRE后可在尿液中检测到TMPRSS2-ERG融合转录本,灵敏度为37%。在该患者队列中,基于PCA3的检测法灵敏度为62%。当两种标志物联合使用时,灵敏度提高到73%。特别是在血清前列腺特异性抗原水平持续升高且活检阴性的男性队列中,TMPRSS2-ERG融合转录本94%的高阳性预测值能更好地指示哪些患者需要重复活检。

结论

在本报告中,我们首次使用前列腺癌特异性生物标志物TMPRSS2-ERG和PCA3的联合检测,这显著提高了前列腺癌诊断的灵敏度。

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