本文選題：前列腺癌 + 尿PCA3評分　； 參考：《吉林大學》2014年博士論文

【摘要】：前列腺癌是當今社會影響男性健康的最常見的惡性腫瘤之一，對男性健康的威脅逐年增加，，其發(fā)病率與死亡率分別高居世界男性惡性腫瘤的第2位和第6位。在美國，前列腺癌的發(fā)病率已經(jīng)超過肺癌，成為威脅男性健康的主要的惡性腫瘤。與歐美發(fā)達國家相比，亞洲人群前列腺癌的發(fā)病率較低。我國曾被認為是前列腺癌的低發(fā)國家，但是隨著國內(nèi)人口老齡化步伐的加快、飲食習慣的西方化以及前列腺癌診治水平的不斷提高，我國前列腺癌的發(fā)病率正逐年上升。據(jù)資料統(tǒng)計，2009年前列腺癌的發(fā)病率及死亡率與2003年比較，分別升高了51.91%和64.96%。現(xiàn)階段，在臨床上廣泛應用于前列腺癌篩查的實驗室檢查是測定血清PSA的水平。但PSA無前列腺癌特異性，由于前列腺炎、急性尿潴留、膀胱鏡檢查、導尿和直腸指診等，均可能會造成血清PSA水平增高，導致診斷的特異性降低。因此，臨床上迫切需要尋找一種新的前列腺癌特異性腫瘤標志物，以便提高早期前列腺癌的診斷率。 PCA3為前列腺癌特異性基因，在前列腺癌組織中高表達，在正常前列腺組織中不表達或低表達，在非前列腺癌的癌組織中不表達。隨著近幾年對于PCA3的研究，發(fā)現(xiàn)尿PCA3評分對于前列腺癌的診斷具有極高的價值可以為血清PSA升高的患者是否需行前列腺穿刺活檢，以及對于初次活檢陰性的患者是否需行二次前列腺穿刺活檢提供依據(jù)。但是，在血清PSA灰區(qū)范圍內(nèi)，尿PCA3評分在診斷早期前列腺癌的應用價值尚無大宗病例報道。基于以上原因，本實驗通過細胞培養(yǎng)、RNA提取、逆轉錄、酶聯(lián)免疫、RNA凝膠電泳、HE染色、免疫組化及RT-qPCR等實驗技術，從而明確尿PCA3評分在血清PSA灰區(qū)內(nèi)診斷早期前列腺癌的意義。 研究結果： 1、在細胞學層面研究，應用RT-qPCR技術得出前列腺癌細胞株LNCaP的PCA3的基因表達量為72.21±42.43；正常前列腺上皮細胞株RWPE-1的PCA3的基因表達量為9.35±6.72；膀胱癌細胞株T24中，無PCA3基因的表達。PCA3基因表達量在前列腺癌細胞株LNCaP與正常前列腺上皮細胞株RWPE-1比較，有顯著性差異（P=0.0002），說明PCA3mRNA高表達于前列腺癌細胞中。 2、應用RT-qPCR技術，得出尿PCA3評分在不同分組中的表達量：前列腺癌組為164.84±133.24，良性前列腺增生組為31.41±12.42，健康對照組為15.37±8.10。前列腺癌組的尿PCA3評分分別與良性前列腺增生組和健康對照組的尿PCA3評分比較，P值均小于0.000，差異具有統(tǒng)計學意義，說明前列腺癌組的尿PCA3評分明顯高于良性前列腺增生組及健康對照組；并且，尿PCA3評分經(jīng)ROC曲線分析，將截斷值定為47.8時，敏感度和特異度分別為74.3%和89.0%，陽性預測者值和陰性預測值分別為73.3%和90.1%。 3、通過血PSA檢測及排除標準，共有243名血清PSA在4~10ng/ml的患者入組。其中經(jīng)病理學診斷為前列腺癌的患者為22名，良性前列腺增生的患者為221名。以47.8為尿PCA3評分截斷值時，尿PCA3評分陽性表達的為23人，陰性表達的為220人。在22名前列腺癌患者中，尿PCA3評分陽性表達的17例，陰性表達的5例，在221例前列腺增生的患者中，尿PCA3評分陽性表達的6例，陰性表達的215例。尿PCA3評分在血清PSA灰區(qū)范圍內(nèi)診斷前列腺癌的敏感性和特異性分別為77.3%和97.3%，陽性預測值和陰性預測值分別為73.9%和97.7%。對于尿PCA3評分為陽性表達的6例前列腺增生患者，在1個月后再次行前列腺穿刺活檢，另有2例診斷為前列腺癌。其余4例患者隨訪1年，分別于二次穿刺活檢后3個月、6個月、9個月及12個月各檢測1次血清PSA，因血清PSA未見明顯升高，建議繼續(xù)隨診觀察。 研究結論： 1、PCA3基因特異性的高表達于前列腺癌細胞，在正常前列腺上皮細胞呈低表達，在非前列腺癌細胞的其他癌細胞中不表達。 2、尿PCA3評分對于前列腺癌的診斷，具有很高的敏感性和特異性。 3、本實驗中，以47.8作為尿PCA3評分的截斷值，對于診斷前列腺癌具有較高的敏感度、特異度、陽性預測值和陰性預測值。 4、尿PCA3評分在血清PSA灰區(qū)范圍內(nèi)可以提高早期前列腺癌的診斷率； 5、尿PCA3評分對于二次前列腺穿刺活檢具有明確的指導意義。 總之，在血清PSA位于灰區(qū)范圍內(nèi)的患者，同時結合尿PCA3評分的檢測，選擇合適的尿PCA3評分截斷值進行判斷，不僅可以避免不必要的經(jīng)直腸超聲引導下的前列腺穿刺活檢，降低患者的痛苦，而且可以協(xié)助提高早期前列腺癌的診斷率，減少漏診，防止疾病的進展影響患者的預后。因此，尿PCA3評分在血清PSA灰區(qū)范圍內(nèi)診斷早期前列腺癌具有顯著性的意義。
[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 鹵 42.43 , which was obtained by RT - qPCR .
The expression of PCA3 of normal prostate epithelial cell line RWPE - 1 was 9.35 鹵 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 鹵 133.24 , the benign prostatic hyperplasia group was 31.41 鹵 12.42 , the healthy control group was 15.37 鹵 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 .

【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R737.25

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