The Value Of Urinary PCA3Score On Diagnosis Of The Early Prostate Cancer In The PSA Gray Zone

Prostate cancer (PCa) is considered one of the most common malemalignant tumor nowadays. The threatens from PCa have been increasing yearby year. The morbidity and mortality ranks No.2and No.6around the world. InU.S., the morbidity of PCa has already exceeded lung cancer and proved to bethe top malignant tumor threatening male health. Asian populations, includingChinese, used to be regarded with lower morbidities of PCa, comparing with thepopulations in Europe and U.S.. The morbidity and mortality of PCa in year2009were51.91%and64.96%higher than those in year2003. Prostate specificantigen (PSA) test is widely used in clinical screening PCa. However, PSA canhardly be deemed as PCa specific. Many factors such as prostate inflammation,acute retention of urine, cystoscope examination, catheterization and rectaltouch can lead to the increase in serum PSA levels. The misunderstanding of theresults of PSA levels can severely disrupt the clinical diagnosis. Therefore, anovel PCa specific marker is required for more effective early diagnosis.Prostate cancer antigen3(PCA3), a PCa specific gene, has been found withhigh expression in PCa tissues, extremely low expression in healthy prostatetissues and usually no expression in non prostate tissues. PCA3score offers avaluable evidence on whether a prostate biopsy is necessary for the patient with increased serum PSA level or the patient with negative prostate biopsy results.Until now, no studies has ever shown PCA3score has been largely adopted toevaluate serum PSA gray zone. In our research, we try to elucidate the roles ofPCA3score in diagnose of early PCa within serum PSA gray zone by series oftechnologies such as cell culture, RNA preparation, reverse transcription, ELISA,RNA electrophoresis, HE staining, immunohistology and RT-qPCR.Results:1. The expression level of PCA3in LNCap cell line was significantly lowerthan that in RWPE-1(72.21±42.43vs.9.35±6.72, P=0.0002). No PCA3wasexpressed in T24cell line. The result indicates PCA3mRNA is highly expressedin PCa cells.2. The urinary PCA3score of PCa group was significantly higher than thatof benign prostate hyperplasia group and control group (164.84±133.24vs.31.41±12.42, p <0.05;164.84±133.24vs.15.37±8.10, p <0.000; respectively).The results indicate that PCa group has a obviously higher PCA3score thanbenign prostate hyperplasia group and control group. Furthermore, in the ROCanalyze of PCA3score, when the ROC cut-off is47.8, the sensitivity andspecificity are74.3%and89.0%, meanwhile the positive and negative predictivevalue are73.3%and90.1%.3. We have identified243patients within serum PSA gray zone after serumPSA test and samples exclusion.22out of243have been pathologicallydiagnosed as PCa and the rest221were benign prostate hyperplasia (BPH) patients. Out of all243patients,23cases had urinary PCA3score positiveexpressions when ROC cut-off value was set as47.8, and221cases had urinaryPCA3score negative expressions. Out of22PCa patients,17cases had urinaryPCA score positive expressions, while5cases had urinary PCA score negativeexpressions. Out of221BPH patients,6cases had urinary PCA score positiveexpressions, and the rest215cases were negative expressions. The sensitivityand specificity of urinary PCA3score in diagnosing early PCa within gray zoneare77.3%and97.3%. The positive and negative predictive values are73.9%and97.7%. After1month, biopsy results of6BPH patients with uriniary PCA3score positive expression showed2cases had been diagnosed as PCa. The serumPSA levels of the rest4patients after3,6,9and12months showed no credibleincrease, therefore it was suggested to keep on follow-up visits.Conclusions:1. PCA3is highly and specifically expressed in PCa cells. The expressionlevel in healthy prostate cells is low. No PCA3is found being expressed in nonPCa cells.2. Urinary PCA3score is highly sensitive and specific for diagnosing earlyprostate cancer.3. In our study,47.8has been proved to be a proper urinary PCA3scorecut-off value with high sensitivity, specificity, positive and negative predictionfor diagnosis of early PCa.4. Urinary PCA3score is able to raise the effects of diagnosis of early PCa within serum PSA gray zone.5. The second biopsy test can be suggested by urinary PCA3score.In conclusion, PCA3score with proper cut-off value is beneficial inavoiding unnecessary painful biopsy and raising effects of diagnosis of earlyPCa. A good prognosis is believed to be predicted under the suggestion of PCA3score. Thus, PCA3score has positive effects in the diagnosis of early PCa withinserum PSA gray zone.