Application Of Prostate Cancer Susceptibility Candidate And Prostate Cancer Antigen 3 MRNA In Urine Exosomes In The Diagnosis Of Prostate Cancer

【Objective】In China,the incidence of prostate cancer has risen rapidly,and it has become the first malignant tumor of the male urogenital system,which seriously threatens the lives of men.At present,prostate biopsy is still the gold standard for the diagnosis of prostate cancer.However,at the same time,due to the low specificity of prostate-specific antigens and excessive application of biopsy indications,many unnecessary prostate biopsies have been performed.Prostate biopsy is a painful and invasive procedure,which may bring some serious complications such as bleeding and infection.Therefore,the development of new prostate cancer-specific markers is imminent,with the aim of being able to find clinically significant patients with prostate cancer while avoiding a large number of unnecessary biopsies.In this study,we detected the PCA3 and PRAC mRNA in urine exosomes,compared their expression differences in patients with benign prostatic hyperplasia and prostate cancer,and explore the diagnostic value of urine exosome PCA3 / PRAC index in prostate cancer and high-grade prostate cancer in Chinese low PSA population.Identify high-grade and low-grade prostate cancer before puncture biopsy through urine exosome detection,in order to reduce some unnecessary biopsies.【Materials and methods】A total of 57 cases of morning urine before biopsy due to elevated serum PSA and/or abnormal digital rectal examination(serum PSA <20ng / ml)were collected.Patients were divided into benign prostatic hyperplasia group(n=43)and prostate cancer group(n=14)based on the final results of prostate biopsy.According to Gleason score,the prostate cancer group was further divided into high-grade prostate cancer group(Gleason score≥7,n=8)and low-grade prostate cancer group(Gleason score=6,n=6).Exosomes was isolated from patients’ urine by ultra-speed centrifugation,total RNA was extracted from exosomes,then c DNA was synthesized from the harvested total RNA by reverse transcription.PRAC and PCA3 genes were detected in urine exosomes by using real-time quantitative PCR,the relative expression of genes was calculated according to the 2-ΔΔCt method.The Mann-Whitney U test was used to compare the relative expression level of PCA3 and PRAC mRNA and PCA3/PRAC index in urine exosomes between different groups.ROC curve analysis was used to evaluate the diagnostic value of urine exosome PCA3/PRAC index for prostate cancer and high-grade prostate cancer,respectively.【Results】1.Real-time quantitative PCR experiments showed that the relative expression level of urine exosome PCA3 mRNA in the prostate cancer group and benign prostatic hyperplasia group were 16.27±6.70 and 9.21±2.06,p=0.45;in grade prostate cancer group,low grade prostate cancer group and benign prostatic hyperplasia group they were 24.88 ± 10.82,4.78 ± 2.73 and 9.21 ± 2.06,the difference between high grade prostate cancer group and benign prostatic hyperplasia group did not reach statistical significance(p=0.08).The relative expression level of PRAC mRNA in urine exosomes in prostate cancer group and benign prostatic hyperplasia group were 2.52 ± 0.69 and11.32±2.67,respectively,p=0.014;in high-grade prostate cancer group and low-grade prostate cancer group and benign prostatic hyperplasia group they were 3.74 ± 1.05,1.10 ± 0.39 and 11.32 ± 2.67,the difference between the high-grade prostate cancer group and benign prostatic hyperplasia group did not reach statistical significance(p=0.39).Urine exosome PCA3/PRAC index in prostate cancer group and benign prostatic hyperplasia group were 119.84±29 and 80.19±23.02,p=0.01;in high-grade prostate cancer group and low-grade prostate cancer group and benign prostatic hyperplasia group they were 133.55 ± 44.69,101.57 ± 35.47 and 80.19 ± 23.02,the difference between the high-grade prostate group and benign prostatic hyperplasia was significant,p=0.02.2.When using ROC curve analysis,the AUC of urine exosome PCA3/PRAC index was higher than that of serum PSA(0.723 vs 0.595)in the diagnosis of prostate cancer,and the AUC of urine exosome PCA3/PRAC index in the diagnosis of high-grade prostate cancer was also higher than blood PSA(0.736 vs 0.529).When using 5 as urine exosome PCA3/PRAC index cut-off point,the sensitivity,specificity,negative predictive value and positive predictive value of high-grade prostate cancer were: 100%,57.1%,100%,27.59%,respectively.【Conclusions】1.The expression level of PCA3 mRNA in urine exosomes in patients with prostate cancer and high-grade prostate cancer is higher than that in patients with benign prostatic hyperplasia;the expression level of PRAC mRNA in urine exosomes in benign prostatic hyperplasia is higher than that in prostate cancer group and high-grade prostate cancer group;the urine exosomes PCA3/PRAC index in patients with prostate cancer and high-grade prostate cancer is significantly higher than that in benign prostatic hyperplasia group.2.The use of urine exosome PCA3/PRAC index can effectively identify high-grade prostate cancer patients before prostate biopsy and may reduce unnecessary prostate biopsy in the remaining patients.