Detection of Prostate Cancer Antigen 3 and Prostate Cancer Susceptibility Candidate in Non-DRE Urine Improves Diagnosis of Prostate Cancer in Chinese Population.

Lie-Fu Ye,Ruo-Chen Zhang,Dan-Ling Pan,Gang Li,Xiaopei Wu,Ze-Song Yang,Shengying Jiang,Fa-Wen Chen,Dong Li,Sha He

doi:10.1155/2020/3964615

Abstract

Although prostate biopsy is the gold standard for the diagnosis of prostate cancer, it also leads to high incidence of negative biopsies and the diagnosis of clinically low-risk prostate cancer and the subsequent overtreatment. It remains an unmet need to discover new biomarkers in order to defer the unnecessary biopsies in clinical practice. In this study, we described a new method, LBXexo score, to measure the urine exosomal PCA3/PRAC expression from non-DRE urine as a noninvasive diagnosis to improve the detection rate in Chinese population with a low serum PSA level. First-voided urine samples were collected to isolate exosomes, and exosomal RNAs of PCA3 and PRAC were measured by quantitative reverse transcription PCR. A significant increase in exoPCA3/PRAC was observed in both any-grade and high-grade prostate cancer groups when compared with the biopsy-negative group. Receiver-operating characteristic curve analyses showed that the LBXexo score significantly improved diagnostic performance in predicting biopsy results, with AUCs of 0.723 (p=0.017) and 0.736 (p=0.038) for any-grade and high-grade (GS ≥ 7) prostate cancer, respectively. For high-grade cancer, LBXexo had the negative and positive predictive values of 100% and 27.59%, respectively, and could potentially avoid unnecessary biopsy. This is the first report in Chinese population that demonstrates the predictive value of the exosomal expression of PCA3 and PRAC derived from non-DRE urine in predicting prostate biopsy outcomes. It could be used in clinical practice to make a better informed biopsy decision and avoid unnecessary biopsies in Chinese population.

Highlights

Prostate cancer (PCa) is the most frequently diagnosed cancer and the second-leading cause of cancer death in male worldwide, with almost 1.3 million new cases diagnosed and 359,000 deaths in 2018 [1]
We reported for the first time the combination of Prostate cancer antigen 3 (PCA3) and prostate cancer susceptibility candidate (PRAC) gene expressions in exosomes isolated from non-digital rectal exam (DRE) urine samples as a noninvasive test in predicting biopsy outcomes in Chinese population
Samples were collected in a standard urine collection cup and delivered on ice to a central laboratory at Fujian Provincial Hospital for initial processing. e urine samples were centrifuged at 5000 rpm for 15 min at 4°C to remove debris, filtered through a 0.8 μm syringe filter, and stored in 30 ml aliquots at − 80 C until further processing

Summary

Introduction

Prostate cancer (PCa) is the most frequently diagnosed cancer and the second-leading cause of cancer death in male worldwide, with almost 1.3 million new cases diagnosed and 359,000 deaths in 2018 [1]. With economic growth and lifestyle change, prostate cancer is the most rapidly increasing male cancer in China, and it is currently the sixth common cancer in men with approximate 60,300 new cases in 2015 [2]. Prostate needle biopsy is still the gold standard for definitive diagnosis for patients with elevated serum PSA and suspicious digital rectal exam (DRE) together with age and family history. Due to low specificity of PSA and high prevalence of low-risk PCa, more than 70% of patients are unnecessarily biopsied [4].

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