Estradiol metabolites as biomarkers of endometrial cancer prognosis after surgery
Estradiol metabolites as biomarkers of endometrial cancer prognosis after surgery
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DOI：
10.1016/j.jsbmb.2017.10.021
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发表时间：
2018-04-01
影响因子：
4.1
通讯作者：
Guillemette, Chantal
中科院分区：
文献类型：
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作者：
Audet-Delage, Yannick;Gregoire, Jean;Guillemette, Chantal
子宫内膜癌(EC)是绝经后最常见的妇科恶性肿瘤。确定类固醇类型可能有助于预测子宫切除术后复发的风险，由于缺乏可靠的标记物，这一风险仍然有限。对246例新诊断的绝经后EC患者行术前和子宫切除术后1个月的血清，用质谱仪(MS)测定肾上腺前体、雄激素、母体雌激素和儿茶酚雌激素代谢产物。我们还调查了110名健康的绝经后妇女，研究了类固醇激素和EC状态之间的关系。分析激素浓度与临床病理特征、复发和总生存期(OS)的关系。平均随访时间65.5个月，26例术后复发，复发率为10.6%(I型6.4%，II型29.5%)。复发和OS与更具侵袭性的疾病有关，但与体重指数无关。多因素Logistic回归分析显示，术前血清雌三醇(E-3)和硫酸雌酮(ERS)水平与复发呈负相关(危险比分别为0.31P=0.039和3.01P=0.024)。除4-甲氧基-E-2(4-MeO-E-2)外，术后所有循环类固醇激素水平均显著下降，接近健康女性的水平，术后4-甲氧基-E-2水平升高35%，复发风险降低68%(HR=0.32，P=0.015)。诊断为这两种组织学类型的EC的妇女表现出显著更高的类固醇水平，以支持其促有丝分裂作用。雌激素前体E-L-5、抗癌代谢产物4MeO-E-2和E-3具有混合的拮抗剂和激动剂雌激素活性和免疫效应，是潜在的独立预后因素。
Endometrial cancer (EC) is the most common gynecologic malignancy prevailing after menopause. Defining steroid profiles may help predict the risk of recurrence after hysterectomy, which remains limited due to the lack of reliable markers. Adrenal precursors, androgens, parent estrogens and catechol estrogen metabolites were measured by mass spectrometry (MS) in preoperative serums and those collected one month after hysterectomy from 246 newly diagnosed postmenopausal EC cases. We also examined the associations between steroid hormones and EC status by including 110 healthy postmenopausal women. Steroid concentrations were analyzed in relation to clinicopathological features, recurrence and overall survival (OS). The mean follow-up time was 65.5 months and 26 patients experienced relapse after surgery for a recurrence incidence of 10.6% (6.4% Type I and 29.5% Type II). Recurrence and OS were related to a more aggressive disease but not linked to body mass index. Preoperative levels of estriol (E-3) and estrone-sulfate (ErS) were inversely associated with recurrence in a multivariate logistic regression analysis (Hazard ratios (HRs) of 0.31, P = 0.039 and 3.01, P = 0.024; respectively). All circulating steroids declined considerably after surgery almost reaching those of healthy women, except 4-methoxy-E-2 (4MeO-E-2) for which postoperative levels increased by 35% and were associated to a 68% decreased risk of recurrence (HR = 0.32, P = 0.015). Women diagnosed with both histological types of EC present significantly higher levels of steroids, in support of their mitogenic effects. The estrogen precursor E-l-5, theanticancer metabolite 4MeO-E-2, and E-3 that exert mixed antagonist and agonist estrogenic activities and immunological effects, are potential independent prognostic factors.