School of Biological Sciences & Medical Engineering, Southeast University, Nanjing 210096, China.
Department of Dermatology, the Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
Clin Chim Acta. 2022 Jun 1;531:389-398. doi: 10.1016/j.cca.2022.04.995. Epub 2022 Apr 27.
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.
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).
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%.
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.
尽管它们参与了前列腺癌的进展，但性类固醇激素在尿外泌体中的应用作为前列腺癌的生物标志物仍然不清楚。在这里，研究了尿外泌体中性类固醇激素作为生物标志物在预测早期前列腺癌中的潜在用途，以协助临床诊断。
随机招募了 286 名参与者，其中 231 名前列腺癌患者和 55 名健康对照者。根据他们的 Gleason 评分（GS），将前列腺癌患者分为两组，轻度前列腺癌（GS6）（n=116）和重度（≥GS7）组（n=115）。使用液相色谱串联质谱法结合大气压化学电离（LC-APCI-MS/MS）定量测定尿外泌体中 8 种性激素的浓度。
结果表明，8 种性激素中的 7 种（脱氢表雄酮（DHEA）、脱氢表雄酮硫酸盐（DHEAS）、雄烯二酮（A4）、睾酮（T）、孕酮（P）、二氢睾酮（DHT）和雌酮（E1）），但不是尿外泌体中的雌二醇（E2），不仅能将前列腺癌患者与健康对照者区分开来，还能区分轻度和重度前列腺癌患者。在 8 种选定的尿外泌体生物标志物中，最终筛选了 DHEA、DHEAS、T 和 DHT 进一步构建回归模型，并且 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%。
我们的数据首次表明，尿中外泌体性激素可用作预测前列腺癌的生物标志物。这一发现将为前列腺癌的诊断提供新的见解。
