Centre Hospitalier Universitaire de Québec (CHU de Québec) Research Center, Cancer Research Center (CRC) of Université Laval and Faculty of Pharmacy, Université Laval, Québec, QC, Canada.
Statistical and Clinical Research Platform, CHU de Québec Research Center, Québec, QC, Canada.
Front Endocrinol (Lausanne). 2023 May 23;14:1156680. doi: 10.3389/fendo.2023.1156680. eCollection 2023.
Recent evidence support that androgens play an important role in the etiology of endometrial cancer (EC). Adrenal-derived 11-oxygenated androgens are highly potent agonists of the androgen receptor (AR), comparable to testosterone (T) and dihydrotestosterone (DHT) that have not been studied in the context of EC.
We studied a cohort of 272 newly diagnosed postmenopausal EC cases undergoing surgical treatment. Circulating concentrations of seven 11-oxygenated androgens including precursors, potent androgens and their metabolites were established in serum samples collected before and 1 month after surgery using a validated liquid chromatography tandem mass spectrometry method (LC-MS/MS). Free (unconjugated) and total (free + sulfate and glucuronide conjugates following enzymatic hydrolysis) were analyzed in relation to clinicopathological features, recurrence and disease-free survival (DFS).
Levels of 11-oxygenated androgens were weakly correlated to those of canonical androgens such as testosterone (T) and dihydrotestosterone (DHT), with no evidence of their association with clinicopathological features. Levels of 11-oxygenated androgens declined after surgery but remained higher in overweight and obese compared to normal weight cases. Higher levels of preoperative free 11-ketoandrosterone (11KAST) were associated with an increased risk of recurrence (Hazard ratio (HR) of 2.99 (95%CI=1.09-8.18); =0.03). Postoperative free 11β-hydroxyandrosterone (11OHAST) levels were adversely associated with recurrence and DFS (HR = 3.23 (1.11-9.40); =0.03 and 3.27 (1.34-8.00); =0.009, respectively).
11-oxygenated androgen metabolites emerge as potential prognostic markers of EC.
最近的证据表明，雄激素在子宫内膜癌（EC）的发病机制中起着重要作用。肾上腺衍生的 11-氧化雄激素是雄激素受体（AR）的高效激动剂，与未在 EC 背景下研究过的睾酮（T）和二氢睾酮（DHT）相当。
我们研究了 272 例新诊断的绝经后接受手术治疗的 EC 病例队列。在手术前和手术后 1 个月，使用经过验证的液相色谱串联质谱法（LC-MS/MS）在血清样本中建立了七种 11-氧化雄激素（包括前体、强效雄激素及其代谢物）的循环浓度。分析游离（未结合）和总（游离+酶水解后的硫酸盐和葡萄糖醛酸缀合物）与临床病理特征、复发和无病生存（DFS）的关系。
11-氧化雄激素的水平与经典雄激素（如睾酮（T）和二氢睾酮（DHT））的水平呈弱相关，没有证据表明它们与临床病理特征有关。11-氧化雄激素水平在手术后下降，但在超重和肥胖患者中仍高于正常体重患者。术前游离 11-酮雄烯二酮（11KAST）水平较高与复发风险增加相关（风险比（HR）为 2.99（95%CI=1.09-8.18）；=0.03）。术后游离 11β-羟基雄烯二酮（11OHAST）水平与复发和 DFS 呈负相关（HR=3.23（1.11-9.40）；=0.03 和 3.27（1.34-8.00）；=0.009，分别）。
11-氧化雄激素代谢物成为 EC 的潜在预后标志物。
