PCA3评分对前列腺癌早期诊断的临床意义

发布时间：2018-05-19 23:22

  本文选题：前列腺癌 + 前列腺癌基因3　； 参考：《天津医科大学》2014年硕士论文

【摘要】：目的：1.探讨前列腺癌和良性前列腺增生患者尿液中PCA3mRNA相对表达水平及尿PCA3评分诊断前列腺癌的应用价值(敏感性、特异性等)；2.探讨尿液不同PCA3评分的截断值对可疑前列腺癌患者诊断的应用价值；3.探讨PCA3评分与前列腺癌病理分级的相关性及其在前列腺癌治疗和监测中的意义。 方法：收集2011年12月至2013年3月在天津医科大学第二医院因血清PSA升高和(或)DRE异常住院行B超引导下经直肠前列腺穿刺活检的患者。采集前列腺按摩后的初始段尿液标本,采用细胞分离、RNA提取、RT-PCR、琼脂糖凝胶电泳和实时定量PCA等技术,检测尿沉渣中PSA及PCA3mRNA的表达,测定穿刺前尿样PCA3的评分。结合穿刺的病理结果应用ROC曲线比较血tPSA、%f/PSA与尿PCA3评分对前列腺癌诊断的准确性。比较不同尿PCA3评分的截断值对诊断前列腺癌的敏感性和特异性(阳性预测和阴性预测),并确定最佳截断值。分析尿PCA3评分与Gleason评分的相关性,探讨PCA3评分在前列腺癌治疗及监测中的意义。 结果：1.本次研究共收集153例患者的尿标本,123例(80.4%)成功分离出可疑前列腺癌患者尿中的前列腺脱落细胞,并成功检测了穿刺前PSA和PCA3mRNA的含量,后经前列腺穿刺活检后证实前列腺癌32例,前列腺良性增生91例。前列腺癌组年龄52～88岁,平均69岁；PSA:6.9-40.8ng4nl,平均12.7ng4nl。前列腺良性增生组年龄57～86岁,平均65岁；PSA:6.0-36.5ng4nl,平均7.6ng/PSA前列腺癌患者尿液标本中PCA3mRNA相对表达水平较良性前列腺增生患者尿液标本表达增高,差异具有统计学意义。前列腺癌患者尿液中PCA3评分平均为63±71,前列腺增生患者尿液中PCA3评分平均为24±27,前列腺癌组PCA3评分明显高于前列腺增生组,且差异具有统计学意义(P0.05)。通过ROC曲线比较tPSA、%f/PSA与PCA3评分对前列腺癌诊断的准确性,PCA3评分ROC-AUC=0.734(95%CI:0.656～0.811), PSAROC-AUC=0.606(95%CI:0.526-0.692)。 PCA3评分的诊断准确性优于PSA,差异具有显著的统计学意义(P0.05);%fPSAROC-AUC=0.621(95%CI:0.552～0.712)。 PCA3评分的诊断准确性优于%f/PSA,差异显著具有统计学意义(P0.05)。 2.经穿刺病理结果证实前列腺癌32例,前列腺良性增生91例。当PCA3截断值分别取35、50时,其敏感性分别是78.1%、65.5%,特异性分别是69.8%、82.1%,阳性预测值分别是52.1%、59.7%,阴性预测值分别是87.7%、83.4%,PCA3检测诊断准确性分别是72.8%和75.6%。当设定PCA3评分截断值为35,91例患者中可避免48例(52.7%)进行不必要的穿刺,8.8%(8例)的患者被漏诊(被漏诊的患者均是低危前列腺癌)：当设定PCA3评分截断值为50时,91例患者中66例(72.5%)可避免进行不必要的穿刺,但13.2%(12例)的患者被漏诊,且2例(16.7%)是中高危前列腺癌。结果显示,PCA3评分35是最佳截断值,其既可以减少较多不必要的穿刺,同样也不会使中高危前列腺癌漏诊。且在PSA水平4～10ng/ml区间,PCA3评分35仍有较高的诊断准确性,其诊断敏感性和特异性分别是76.6%和64.5%。 3.穿刺结果显示Gleason评分7组有15例患者,Gleason评分≥7组有17例患者,在不同Gleason评分的前列腺癌患者中PCA3评分差异的比较结果显示Gleason评分≥7组PCA3评分为81±89；7组为56±61.两组差异有统计学意义(P0.05),并存在正相关趋势(P0.05)。说明前列腺癌Gleason评分的高低可能与PCA3基因表达有关。 结论：1.前列腺癌患者尿液标本中PCA3mRNA相对表达水平较良性前列腺增生患者尿液标本中PCA3mRNA相对表达增高,且前列腺癌患者组平均PCA3评分明显高于前列腺增生组。 2.与血PSA相比,尿PCA3评分敏感性稍低,但具有很好的特异性和阳性预测值,在PSA介于灰色区域4～10ng/ml时,穿刺结果阳性率较低,尿PCA3评分诊断PCa的特异性达64.5%,可能能够协助判断是否需要穿刺活检,且增加穿刺阳性率。通过ROC曲线分析PCA3评分对前列腺癌的检出率明显高于血PSA对前列腺癌的检出率。PCA3评分对穿刺结果的预测效能要高于PSA,它可能是更为理想的前列腺癌特异性标志物,能减少不必要的前列腺穿刺活检。 3.中高危前列腺癌组的PCA3评分高于低危前列腺癌组的PCA3评分,且PCA3评分与前列腺癌Gleason评分具有正相关性,说明可能前列腺癌Gleason评分的高低,与PCA3基因表达有关,检测PCA3评分有望成为PCa治疗监测中的良好指标。
[Abstract]:Objective : To investigate the relative expression level of PCA3 mRNA in urine of patients with prostate cancer and benign prostatic hyperplasia ( BPH ) and the application value ( sensitivity , specificity , etc . ) of PCA3 in diagnosing prostate cancer .
2 . To investigate the value of the cutoff value of different PCA3 scores in the diagnosis of suspicious prostate cancer patients .
3 . To investigate the correlation between the PCA3 score and the pathological grade of prostate cancer and its significance in the treatment and monitoring of prostate cancer .

Methods : The patients who underwent transrectal prostate biopsy were collected from December 2011 to March 2013 in the second hospital of Tianjin Medical University . The results were as follows : Cell separation , RNA extraction , RT - PCR , agarose gel electrophoresis and real - time quantitative PCA were used to measure the accuracy of the diagnosis of prostate cancer . The correlation between the score of the PCA3 and Gleason score was compared . The significance of the PCA3 score in the treatment and monitoring of prostate cancer was discussed .

Results : 1 . The urine samples of 153 cases were collected in this study , 123 cases ( 80.4 % ) successfully separated the prostate exfoliated cells in urine of patients with suspected prostate cancer , and successfully detected the contents of PSA and PCA3 mRNA before puncture , and confirmed 32 cases of prostate cancer and 91 benign prostatic hyperplasia after prostate biopsy .
PSA : 6.9 - 40.8 ng4nl , mean 12.7ng4nl . The benign prostatic hyperplasia group was 57 - 86 years old , the average age was 65 years .
The expression of PCA3 mRNA in urine of patients with prostate cancer was significantly higher than that in benign prostatic hyperplasia ( P 0.05 ) . Compared with the prostatic hyperplasia group , the PCA3 score in urine of patients with prostate cancer was significantly higher than that in benign prostatic hyperplasia group ( P < 0.05 ) . The ROC - AUC was 0.734 ( 95 % CI : 0.656 - 0.811 ) and 0.606 ( 95 % CI : 0.526 - 0.692 ) . The diagnostic accuracy of the PCA3 score was superior to that of PSA , with significant statistical significance ( P0.05 ) ; % fPSAROC - AUC = 0.621 ( 95 % CI : 0.552 - 0.712 ) . The diagnostic accuracy of the PCA3 score was better than that of % f / PSA ( P0.05 ) .

The sensitivity and specificity of the PCA3 were 78.7 % , 83.4 % , 87.7 % , 83.4 % , 87.7 % , 83.4 % , respectively .

3 . The results showed that there were 15 patients in the Gleason score 7 group , 17 patients with Gleason score 鈮，

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