PCA3 in prostate cancer and tumor aggressiveness detection on 407 high-risk patients: a National Cancer Institute experience.

PCA3 in prostate cancer and tumor aggressiveness detection on 407 high-risk patients: a National Cancer Institute experience.
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DOI:
10.1186/s13046-015-0127-8
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发表时间:
2015-02-06
期刊:
Journal of experimental & clinical cancer research : CR
影响因子:
--
通讯作者:
Conti L
Conti L
中科院分区:
其他
文献类型:
--
作者:
Merola R;Tomao L;Antenucci A;Sperduti I;Sentinelli S;Masi S;Mandoj C;Orlandi G;Papalia R;Guaglianone S;Costantini M;Cusumano G;Cigliana G;Ascenzi P;Gallucci M;Conti L

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前列腺癌(PCa)是欧洲和美国最常见的男性癌症。早期诊断依赖于前列腺特异性抗原(PSA)血清检测,即使它显示出明确的限制。在目前正在研究的新测试中,最有希望的是前列腺癌基因3(PCA 3),这是一种非编码mRNA,与正常组织相比,其水平在PCa组织中增加高达100倍。通过本研究,我们有助于验证PCA 3测试的临床实用性,并评估其预后潜力。407名意大利男性,有两个或两个以上的PCa风险因素和至少以前的阴性活检,进入里贾纳埃莱娜国家癌症研究所泌尿科,进行了PCA 3,总PSA(tPSA)和游离PSA(fPSA和f/tPSA)测试。在入组的407名男性中,195名PCa阳性,其中114名接受了准确的Gleason评分(Gs)分期。然后,将PCA 3评分与活检结果进行相关性分析,并评估其诊断和预后价值。在PCA 3检测后进行的407例活检中,195例(48%)结果为PCa阳性;该人群的PCA 3评分显著高于tPSA(p < 0.0001)(p = 0.87)。此外,PCA 3检验优于f/tPSA(p = 0.01)。PCA 3测试的灵敏度(94.9)和特异性(60.1)显示,与阈值20相比,阈值35的平衡更好,即使考虑到截止值51,也能获得最佳结果,灵敏度和特异性分别为82.1%和79.3%。最后,比较两个Gs增加的亚组(Gs ≤ 6 vs Gs ≥ 7)之间的PCA 3检验值,发现PCA 3评分与Gs之间存在显著相关性(p = 0.02)。与tPSA和f/tPSA相比,PCA 3检测显示出最佳的诊断性能,有助于选择可能从饱和前列腺活检中受益的高危患者。此外,PCA 3测试显示出预后价值,因为较高的PCA 3评分值与较大的肿瘤侵袭性相关。
Prostate cancer (PCa) is the most common male cancer in Europe and the US. The early diagnosis relies on prostate specific antigen (PSA) serum test, even if it showed clear limits. Among the new tests currently under study, one of the most promising is the prostate cancer gene 3 (PCA3), a non-coding mRNA whose level increases up to 100 times in PCa tissues when compared to normal tissues. With the present study we contribute to the validation of the clinical utility of the PCA3 test and to the evaluation of its prognostic potential. 407 Italian men, with two or more PCa risk factors and at least a previous negative biopsy, entering the Urology Unit of Regina Elena National Cancer Institute, were tested for PCA3, total PSA (tPSA) and free PSA (fPSA and f/tPSA) tests. Out of the 407 men enrolled, 195 were positive for PCa and 114 of them received an accurate staging with evaluation of the Gleason score (Gs). Then, the PCA3 score was correlated to biopsy outcome, and the diagnostic and prognostic utility were evaluated. Out of the 407 biopsies performed after the PCA3 test, 195 (48%) resulted positive for PCa; the PCA3 score was significantly higher in this population (p < 0.0001) differently to tPSA (p = 0.87). Moreover, the PCA3 test outperformed the f/tPSA (p = 0.01). The sensitivity (94.9) and specificity (60.1) of the PCA3 test showed a better balance for a threshold of 35 when compared to 20, even if the best result was achieved considering a cutoff of 51, with sensitivity and specificity of 82.1% and 79.3%, respectively. Finally, comparing values of the PCA3 test between two subgroups with increasing Gs (Gs ≤ 6 versus Gs ≥ 7) a significant association between PCA3 score and Gs was found (p = 0.02). The PCA3 test showed the best diagnostic performance when compared to tPSA and f/tPSA, facilitating the selection of high-risk patients that may benefit from the execution of a saturation prostatic biopsy. Moreover, the PCA3 test showed a prognostic value, as higher PCA3 score values are associated to a greater tumor aggressiveness.
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