Roberts Matthew J, Chow Clement W K, Schirra Horst Joachim, Richards Renee, Buck Marion, Selth Luke A, Doi Suhail A R, Samaratunga Hema, Perry-Keene Joanna, Payton Diane, Yaxley John, Lavin Martin F, Gardiner Robert A
The University of Queensland, Centre for Clinical Research, Brisbane, Qld, Australia; Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Qld, Australia; The University of Queensland, Centre for Advanced Imaging, Brisbane, Qld, Australia.
Prostate. 2015 Apr 1;75(5):539-49. doi: 10.1002/pros.22942. Epub 2015 Jan 18.
Here, we report on the evaluation of the diagnostic performance of ejaculate-derived PCA3, Hepsin, and miRNAs to complement serum PSA to detect prostate cancer. cDNA was prepared from 152 candidate specimens following RNA isolation and amplification for PSA, PCA3 and Hepsin qPCR, with 66 having adequate RNA for all three assays. Small RNA sequencing and examination of PCa-associated miRNAs miR-200b, miR-200c, miR-375 and miR-125b was performed on 20 specimens. We compared findings from prostate biopsies using D'Amico and PRIAS classifications and in relation to whole gland histopathology following radical prostatectomy. Multivariate logistic regression modeling and clinical risk (incorporating standard clinicopathological variables) were performed for all ejaculate-based markers.
While Hepsin alone was not of predictive value, the Hepsin:PCA3 ratio together with serum PSA, expressed as a univariate composite score based on multivariate logistic regression, was shown to be a better predictor than PSA alone of prostate cancer status (AUC 0.724 vs. 0.676) and risk, using D'Amico (AUC 0.701 vs. 0.680) and PRIAS (AUC 0.679 vs. 0.659) risk stratification criteria as classified using prostate biopsies. It was also possible to analyse a subgroup of patients for miRNA expression with miR-200c (AUC 0.788) and miR-375 (AUC 0.758) showing best single marker performance, while a combination of serum PSA, miR-200c, and miR-125b further improved prediction for prostate cancer status when compared to PSA alone determined by biopsy (AUC 0.869 vs. 0.672; P < 0.05), and risk (D'Amico/PRIAS) as well as by radical prostatectomy histology (AUC 0.809 vs. 0.690). For prostate cancer status by biopsy, at a sensitivity of 90%, the specificity of the test increased from 11% for PSA alone to 67% for a combination of PSA, miR-200c, and miR-125b.
These results show that use of a combination of different types of genetic markers in ejaculate together with serum PSA are at least as sensitive as those reported in DRE urine. Furthermore, a combination of serum PSA and selected miRNAs improved prediction of prostate cancer status. This approach may be helpful in triaging patients for MRI and biopsy, when confirmed by larger studies.
在此，我们报告对精液来源的PCA3、Hepsin和微小RNA（miRNA）的诊断性能评估，以补充血清前列腺特异性抗原（PSA）用于检测前列腺癌。从152份候选标本中提取RNA并进行扩增后制备cDNA，用于PSA、PCA3和Hepsin的定量聚合酶链反应（qPCR），其中66份标本有足够的RNA用于所有三项检测。对20份标本进行了小RNA测序，并检测了与前列腺癌相关的miRNA miR-200b、miR-200c、miR-375和miR-125b。我们比较了前列腺活检结果，采用达米科（D'Amico）和前列腺癌风险评估系统（PRIAS）分类，并与根治性前列腺切除术后的全腺组织病理学结果相关联。对所有基于精液的标志物进行多变量逻辑回归建模和临床风险分析（纳入标准临床病理变量）。
虽然单独的Hepsin没有预测价值，但基于多变量逻辑回归表示为单变量综合评分的Hepsin:PCA3比值与血清PSA一起，被证明比单独的PSA更能预测前列腺癌状态（曲线下面积[AUC] 0.724对0.676）和风险，采用前列腺活检分类的达米科（AUC 0.701对0.680）和PRIAS（AUC 0.679对0.659）风险分层标准。还可以分析一组患者的miRNA表达，其中miR-200c（AUC 0.788）和miR-375（AUC 0.758）表现出最佳的单一标志物性能，而血清PSA、miR-200c和miR-125b的组合与单独通过活检确定的PSA相比，进一步改善了对前列腺癌状态的预测（AUC 0.869对0.672；P < 0.05），以及风险（达米科/PRIAS）和根治性前列腺切除术后组织学结果（AUC 0.809对0.690）。对于通过活检确定的前列腺癌状态，在敏感性为90%时，检测的特异性从单独PSA的11%提高到PSA、miR-200c和miR-125b组合的67%。
这些结果表明，精液中不同类型遗传标志物与血清PSA联合使用至少与直肠指检尿液中报告的一样敏感。此外，血清PSA和选定的miRNA组合改善了对前列腺癌状态的预测。经更大规模研究证实后，这种方法可能有助于对患者进行磁共振成像（MRI）和活检的分流。
