尿PCA3评分在PSA灰区诊断早期前列腺癌意义的研究

发布时间：2018-04-10 19:37

本文选题：前列腺癌 + 尿PCA3评分　；参考：《吉林大学》2014年博士论文

【摘要】：前列腺癌是当今社会影响男性健康的最常见的恶性肿瘤之一，对男性健康的威胁逐年增加，，其发病率与死亡率分别高居世界男性恶性肿瘤的第2位和第6位。在美国，前列腺癌的发病率已经超过肺癌，成为威胁男性健康的主要的恶性肿瘤。与欧美发达国家相比，亚洲人群前列腺癌的发病率较低。我国曾被认为是前列腺癌的低发国家，但是随着国内人口老龄化步伐的加快、饮食习惯的西方化以及前列腺癌诊治水平的不断提高，我国前列腺癌的发病率正逐年上升。据资料统计，2009年前列腺癌的发病率及死亡率与2003年比较，分别升高了51.91%和64.96%。现阶段，在临床上广泛应用于前列腺癌筛查的实验室检查是测定血清PSA的水平。但PSA无前列腺癌特异性，由于前列腺炎、急性尿潴留、膀胱镜检查、导尿和直肠指诊等，均可能会造成血清PSA水平增高，导致诊断的特异性降低。因此，临床上迫切需要寻找一种新的前列腺癌特异性肿瘤标志物，以便提高早期前列腺癌的诊断率。 PCA3为前列腺癌特异性基因，在前列腺癌组织中高表达，在正常前列腺组织中不表达或低表达，在非前列腺癌的癌组织中不表达。随着近几年对于PCA3的研究，发现尿PCA3评分对于前列腺癌的诊断具有极高的价值可以为血清PSA升高的患者是否需行前列腺穿刺活检，以及对于初次活检阴性的患者是否需行二次前列腺穿刺活检提供依据。但是，在血清PSA灰区范围内，尿PCA3评分在诊断早期前列腺癌的应用价值尚无大宗病例报道。基于以上原因，本实验通过细胞培养、RNA提取、逆转录、酶联免疫、RNA凝胶电泳、HE染色、免疫组化及RT-qPCR等实验技术，从而明确尿PCA3评分在血清PSA灰区内诊断早期前列腺癌的意义。研究结果： 1、在细胞学层面研究，应用RT-qPCR技术得出前列腺癌细胞株LNCaP的PCA3的基因表达量为72.21±42.43；正常前列腺上皮细胞株RWPE-1的PCA3的基因表达量为9.35±6.72；膀胱癌细胞株T24中，无PCA3基因的表达。PCA3基因表达量在前列腺癌细胞株LNCaP与正常前列腺上皮细胞株RWPE-1比较，有显著性差异（P=0.0002），说明PCA3mRNA高表达于前列腺癌细胞中。 2、应用RT-qPCR技术，得出尿PCA3评分在不同分组中的表达量：前列腺癌组为164.84±133.24，良性前列腺增生组为31.41±12.42，健康对照组为15.37±8.10。前列腺癌组的尿PCA3评分分别与良性前列腺增生组和健康对照组的尿PCA3评分比较，P值均小于0.000，差异具有统计学意义，说明前列腺癌组的尿PCA3评分明显高于良性前列腺增生组及健康对照组；并且，尿PCA3评分经ROC曲线分析，将截断值定为47.8时，敏感度和特异度分别为74.3%和89.0%，阳性预测者值和阴性预测值分别为73.3%和90.1%。 3、通过血PSA检测及排除标准，共有243名血清PSA在4~10ng/ml的患者入组。其中经病理学诊断为前列腺癌的患者为22名，良性前列腺增生的患者为221名。以47.8为尿PCA3评分截断值时，尿PCA3评分阳性表达的为23人，阴性表达的为220人。在22名前列腺癌患者中，尿PCA3评分阳性表达的17例，阴性表达的5例，在221例前列腺增生的患者中，尿PCA3评分阳性表达的6例，阴性表达的215例。尿PCA3评分在血清PSA灰区范围内诊断前列腺癌的敏感性和特异性分别为77.3%和97.3%，阳性预测值和阴性预测值分别为73.9%和97.7%。对于尿PCA3评分为阳性表达的6例前列腺增生患者，在1个月后再次行前列腺穿刺活检，另有2例诊断为前列腺癌。其余4例患者随访1年，分别于二次穿刺活检后3个月、6个月、9个月及12个月各检测1次血清PSA，因血清PSA未见明显升高，建议继续随诊观察。研究结论： 1、PCA3基因特异性的高表达于前列腺癌细胞，在正常前列腺上皮细胞呈低表达，在非前列腺癌细胞的其他癌细胞中不表达。 2、尿PCA3评分对于前列腺癌的诊断，具有很高的敏感性和特异性。 3、本实验中，以47.8作为尿PCA3评分的截断值，对于诊断前列腺癌具有较高的敏感度、特异度、阳性预测值和阴性预测值。 4、尿PCA3评分在血清PSA灰区范围内可以提高早期前列腺癌的诊断率； 5、尿PCA3评分对于二次前列腺穿刺活检具有明确的指导意义。总之，在血清PSA位于灰区范围内的患者，同时结合尿PCA3评分的检测，选择合适的尿PCA3评分截断值进行判断，不仅可以避免不必要的经直肠超声引导下的前列腺穿刺活检，降低患者的痛苦，而且可以协助提高早期前列腺癌的诊断率，减少漏诊，防止疾病的进展影响患者的预后。因此，尿PCA3评分在血清PSA灰区范围内诊断早期前列腺癌具有显著性的意义。
[Abstract]:Prostate cancer is one of the most common malignant tumors affecting men ' s health in today ' s society . The risk of prostate cancer increases year by year . The incidence rate and mortality rate of prostate cancer in the United States have been higher than those in developed countries .

In recent years , the use of the PCA3 score in the diagnosis of prostate cancer has no major case report . However , in the range of serum PSA ash , the diagnostic value of the urinary PCA3 score in the diagnosis of prostate cancer has no major case report . However , the results of the above reasons indicate that the urinary PCA3 score can be used to diagnose the early prostate cancer by cell culture , RNA extraction , reverse transcription , enzyme - linked immunity , RNA gel electrophoresis , HE staining , immunohistochemistry and RT - qPCR .

Results of the study :

1 . At the cytologic level , the expression of PCA3 gene was 72.21 卤 42.43 , which was obtained by RT - qPCR .
The expression of PCA3 of normal prostate epithelial cell line RWPE - 1 was 9.35 卤 6.72 .
Compared with normal prostate epithelial cell line RWPE - 1 , the expression of PCA3 gene was significantly higher than that of normal prostate epithelial cell line RWPE - 1 ( P = 0 . 0002 ) , suggesting that PCA3 mRNA was highly expressed in prostate cancer cells .

2 . Using RT - qPCR technique , the expression of the urinary PCA3 score in different groups was determined : the prostate cancer group was 164.84 卤 133.24 , the benign prostatic hyperplasia group was 31.41 卤 12.42 , the healthy control group was 15.37 卤 8.10 . The urinary PCA3 score of the prostate cancer group was lower than 0.000 and the difference was statistically significant , indicating that the urinary PCA3 score of the prostate cancer group was significantly higher than that of the benign prostatic hyperplasia group and the healthy control group .
The sensitivity and specificity were 74.3 % and 89.0 % , respectively , and the positive predictive value and negative predictive value were 77.3 % and 90.1 % , respectively .

Among 22 patients with prostatic hyperplasia , the sensitivity and specificity of urinary PCA3 were 77.3 % and 97.7 % , respectively . Among 22 patients with prostate hyperplasia , the sensitivity and specificity of the urinary PCA3 were 77.3 % and 97.7 % , respectively .

Conclusions of the study :

1 . The high expression of the PCA3 gene is expressed in prostate cancer cells and is low in normal prostate epithelial cells , and is not expressed in other cancer cells of non - prostate cancer cells .

2 . The urinary PCA3 score has high sensitivity and specificity for the diagnosis of prostate cancer .

3 . In this experiment , 47.8 was used as the cutoff value of the urinary PCA3 score , which had higher sensitivity , specificity , positive predictive value and negative predictive value for the diagnosis of prostate cancer .

4 . The diagnostic rate of early prostate cancer can be improved in the range of serum PSA gray area .

5 . The urinary PCA3 score has definite guiding significance for secondary prostate biopsy .

In conclusion , in patients with serum PSA located in the gray area , and combined with the detection of the urinary PCA3 score , it can not only avoid unnecessary transrectal ultrasound - guided prostate biopsy , reduce the pain of the patient , but also help to improve the diagnosis rate of early prostate cancer , reduce missed diagnosis and prevent the progression of disease . Therefore , the urinary PCA3 score is of significant significance in the diagnosis of early prostate cancer .

【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R737.25

【参考文献】