背景:尽管它们参与了PCa的进展,泌尿外泌体中的性类固醇激素作为PCa生物标志物的用途仍不清楚.这里,研究了尿液外泌体中的性类固醇激素作为生物标志物的潜在用途,用于预测早期PCa,以协助临床诊断.
方法:随机招募了二百八十六名参与者,231名PCa患者和55名健康对照。根据他们的格里森分数(GS),将PCa患者分为两组,轻度PCa(GS6)组(n=116)和重度(≥GS7)组(n=115)。使用具有大气压化学电离的液相色谱串联质谱法(LC-APCI-MS/MS)定量尿外泌体中8种性类固醇激素的浓度。
结果:结果显示,包括脱氢表雄酮(DHEA)在内的8种性类固醇中的7种水平,脱氢表雄酮(DHEAS),雄烯二酮(A4),睾酮(T),孕酮(P),双氢睾酮(DHT),和雌酮(E1),但不是尿外泌体中的雌二醇(E2),不仅将PCa患者与健康对照区分开来,还可以区分轻度和重度PCa患者。在选定的8个泌尿外泌体生物标志物中,DHEA,DHEAS,T,最后对DHT进行了进一步的筛选,建立了回归模型,4种生物标志物联合检测方法的ROC曲线下面积(AUC)为0.854,预测准确率为78.2%。
结论:我们的数据表明,在尿液中使用外泌体性类固醇可以首次作为预测PCa的生物标志物。这一发现将为PCa诊断提供新的见解。
BACKGROUND: Although they are involved in the progression of PCa, the use of sex steroid hormones in urinary exosomes as biomarkers for PCa remains obscure. Here, the potential use of sex steroid hormones in urinary exosomes as biomarkers was investigated for the prediction of early-stage PCa to assist in clinical diagnosis.
METHODS: Two hundred and eighty-six participants were randomly recruited, 231 patients with PCa and 55 healthy controls. According to their Gleason scores (GSs), the patients with PCa were divided into two groups, mild PCa (GS6) (n = 116) and severe (≥GS7) group (n = 115). The concentrations of 8 sex steroid hormones in urinary exosomes were quantitated using liquid chromatography tandem mass spectrometry with atmospheric pressure chemical ionization (LC-APCI-MS/MS).
RESULTS: The results showed that the levels of 7 out of 8 sex steroids including dehydroepiandrosterone (DHEA), dehydroepiandrosteronesulfate (DHEAS), androstenedione (A4), testosterone (T), progesterone (P), dihydrotestosterone (DHT), and estrone (E1), but not estradiol (E2) in urinary exosomes, were not only distinguished the PCa patients from healthy controls, can also differentiate between patients with mild and severe PCa. Of the 8 selected urinary exosomal biomarkers, DHEA, DHEAS, T, and DHT were finally screened further to build the regression model, and the detection method of the 4 biomarkers-combined achieved an area under the ROC curve (AUC) of 0.854 and predictive accuracy of 78.2%.
CONCLUSIONS: Our data showed the use of exosomal sex steroids in urine could be as biomarkers for predicting PCa for the first time. This finding would supply a novel insight for PCa diagnosis.