本文選題：前列腺癌 + 前列腺癌基因3　； 參考：《天津醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：1.探討前列腺癌和良性前列腺增生患者尿液中PCA3mRNA相對表達(dá)水平及尿PCA3評分診斷前列腺癌的應(yīng)用價值(敏感性、特異性等)；2.探討尿液不同PCA3評分的截斷值對可疑前列腺癌患者診斷的應(yīng)用價值；3.探討PCA3評分與前列腺癌病理分級的相關(guān)性及其在前列腺癌治療和監(jiān)測中的意義。 方法：收集2011年12月至2013年3月在天津醫(yī)科大學(xué)第二醫(yī)院因血清PSA升高和(或)DRE異常住院行B超引導(dǎo)下經(jīng)直腸前列腺穿刺活檢的患者。采集前列腺按摩后的初始段尿液標(biāo)本,采用細(xì)胞分離、RNA提取、RT-PCR、瓊脂糖凝膠電泳和實時定量PCA等技術(shù),檢測尿沉渣中PSA及PCA3mRNA的表達(dá),測定穿刺前尿樣PCA3的評分。結(jié)合穿刺的病理結(jié)果應(yīng)用ROC曲線比較血tPSA、%f/PSA與尿PCA3評分對前列腺癌診斷的準(zhǔn)確性。比較不同尿PCA3評分的截斷值對診斷前列腺癌的敏感性和特異性(陽性預(yù)測和陰性預(yù)測),并確定最佳截斷值。分析尿PCA3評分與Gleason評分的相關(guān)性,探討PCA3評分在前列腺癌治療及監(jiān)測中的意義。 結(jié)果：1.本次研究共收集153例患者的尿標(biāo)本,123例(80.4%)成功分離出可疑前列腺癌患者尿中的前列腺脫落細(xì)胞,并成功檢測了穿刺前PSA和PCA3mRNA的含量,后經(jīng)前列腺穿刺活檢后證實前列腺癌32例,前列腺良性增生91例。前列腺癌組年齡52～88歲,平均69歲；PSA:6.9-40.8ng4nl,平均12.7ng4nl。前列腺良性增生組年齡57～86歲,平均65歲；PSA:6.0-36.5ng4nl,平均7.6ng/PSA前列腺癌患者尿液標(biāo)本中PCA3mRNA相對表達(dá)水平較良性前列腺增生患者尿液標(biāo)本表達(dá)增高,差異具有統(tǒng)計學(xué)意義。前列腺癌患者尿液中PCA3評分平均為63±71,前列腺增生患者尿液中PCA3評分平均為24±27,前列腺癌組PCA3評分明顯高于前列腺增生組,且差異具有統(tǒng)計學(xué)意義(P0.05)。通過ROC曲線比較tPSA、%f/PSA與PCA3評分對前列腺癌診斷的準(zhǔn)確性,PCA3評分ROC-AUC=0.734(95%CI:0.656～0.811), PSAROC-AUC=0.606(95%CI:0.526-0.692)。 PCA3評分的診斷準(zhǔn)確性優(yōu)于PSA,差異具有顯著的統(tǒng)計學(xué)意義(P0.05);%fPSAROC-AUC=0.621(95%CI:0.552～0.712)。 PCA3評分的診斷準(zhǔn)確性優(yōu)于%f/PSA,差異顯著具有統(tǒng)計學(xué)意義(P0.05)。 2.經(jīng)穿刺病理結(jié)果證實前列腺癌32例,前列腺良性增生91例。當(dāng)PCA3截斷值分別取35、50時,其敏感性分別是78.1%、65.5%,特異性分別是69.8%、82.1%,陽性預(yù)測值分別是52.1%、59.7%,陰性預(yù)測值分別是87.7%、83.4%,PCA3檢測診斷準(zhǔn)確性分別是72.8%和75.6%。當(dāng)設(shè)定PCA3評分截斷值為35,91例患者中可避免48例(52.7%)進(jìn)行不必要的穿刺,8.8%(8例)的患者被漏診(被漏診的患者均是低危前列腺癌)：當(dāng)設(shè)定PCA3評分截斷值為50時,91例患者中66例(72.5%)可避免進(jìn)行不必要的穿刺,但13.2%(12例)的患者被漏診,且2例(16.7%)是中高危前列腺癌。結(jié)果顯示,PCA3評分35是最佳截斷值,其既可以減少較多不必要的穿刺,同樣也不會使中高危前列腺癌漏診。且在PSA水平4～10ng/ml區(qū)間,PCA3評分35仍有較高的診斷準(zhǔn)確性,其診斷敏感性和特異性分別是76.6%和64.5%。 3.穿刺結(jié)果顯示Gleason評分7組有15例患者,Gleason評分≥7組有17例患者,在不同Gleason評分的前列腺癌患者中PCA3評分差異的比較結(jié)果顯示Gleason評分≥7組PCA3評分為81±89；7組為56±61.兩組差異有統(tǒng)計學(xué)意義(P0.05),并存在正相關(guān)趨勢(P0.05)。說明前列腺癌Gleason評分的高低可能與PCA3基因表達(dá)有關(guān)。 結(jié)論：1.前列腺癌患者尿液標(biāo)本中PCA3mRNA相對表達(dá)水平較良性前列腺增生患者尿液標(biāo)本中PCA3mRNA相對表達(dá)增高,且前列腺癌患者組平均PCA3評分明顯高于前列腺增生組。 2.與血PSA相比,尿PCA3評分敏感性稍低,但具有很好的特異性和陽性預(yù)測值,在PSA介于灰色區(qū)域4～10ng/ml時,穿刺結(jié)果陽性率較低,尿PCA3評分診斷PCa的特異性達(dá)64.5%,可能能夠協(xié)助判斷是否需要穿刺活檢,且增加穿刺陽性率。通過ROC曲線分析PCA3評分對前列腺癌的檢出率明顯高于血PSA對前列腺癌的檢出率。PCA3評分對穿刺結(jié)果的預(yù)測效能要高于PSA,它可能是更為理想的前列腺癌特異性標(biāo)志物,能減少不必要的前列腺穿刺活檢。 3.中高危前列腺癌組的PCA3評分高于低危前列腺癌組的PCA3評分,且PCA3評分與前列腺癌Gleason評分具有正相關(guān)性,說明可能前列腺癌Gleason評分的高低,與PCA3基因表達(dá)有關(guān),檢測PCA3評分有望成為PCa治療監(jiān)測中的良好指標(biāo)。
[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，

本文編號：1912157