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神经纤维瘤病2型、孕激素受体表达、外源性孕激素的使用与女性眶颅脑膜瘤风险之间的关系

Relationships Between Neurofibromatosis-2, Progesterone Receptor Expression, the Use of Exogenous Progesterone, and Risk of Orbitocranial Meningioma in Females.

作者信息

Supartoto Agus, Sasongko Muhammad Bayu, Respatika Datu, Mahayana Indra Tri, Pawiroranu Suhardjo, Kusnanto Hari, Sakti Dhimas Hari, Nurlaila Prima Sugesty, Heriyanto Didik Setyo, Haryana Sofia Mubarika

机构信息

Department of Ophthalmology, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada-Prof. Dr. Sardjito General Hospital, Yogyakarta, Indonesia.

Department of Biostatistics Epidemiology and Population Health, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

出版信息

Front Oncol. 2019 Jan 9;8:651. doi: 10.3389/fonc.2018.00651. eCollection 2018.

Abstract

The pathogenesis of meningioma in females and its association with exogenous progesterone is remained unclear. This study was aimed to examine expression of Progesterone receptor (PR) and Neurofibromatosis-2 () and assess their relationships to history of exogenous progesterone use and risk of meningioma. Our study was a case-control study that involves 115 females, 40 cases who diagnosed with orbito-cranial meningioma and 75 controls of healthy, that has been presented in previous study. The demographic characteristics, reproductive factors, and history of progesterone use were obtained in-depth face-to-face interviews. PR and mRNA were assessed by real-time quantitative polymerase chain reaction (RT-qPCR) on serum specimens. The mean age of participants in cases vs. controls were 46.6 ± 6.2 vs. 46.5 ± 7.45 ( = 0.969). The expression of PR and in cases was significantly lower than in controls. The longer duration of progesterone exposure was significantly associated with lower expression of PR and . Significant association between lower expression of PR (OR 11.7; 95% CI 4.17-32.9; < 0.001 comparing the lowest quartile vs. 3 highest quartile of PR) and (OR 4.23; 95% CI 1.85-9.67; = 0.001 comparing the 2 lowest quartiles vs. 2 highest quartiles) with increased risk of meningioma were also reported. In this study we showed that the longer the exposure to exogenous progesterone, the lower the expression of PR and mRNA in the serum. Low expression of PR and were associated with higher risk of meningioma, suggesting that low PR expression and inactivation of might play a key role in progesterone-associated meningioma tumorigenesis and may be potential clinical marker for females at higher risk of meningioma.

摘要

女性脑膜瘤的发病机制及其与外源性孕酮的关联仍不清楚。本研究旨在检测孕酮受体(PR)和神经纤维瘤病2型(NF2)的表达,并评估它们与外源性孕酮使用史及脑膜瘤风险的关系。我们的研究是一项病例对照研究,涉及115名女性,其中40例被诊断为眶颅脑膜瘤,75例为健康对照,这些数据已在之前的研究中呈现。通过深入的面对面访谈获取人口统计学特征、生殖因素和孕酮使用史。采用实时定量聚合酶链反应(RT-qPCR)检测血清标本中的PR和NF2 mRNA。病例组与对照组参与者的平均年龄分别为46.6±6.2岁和46.5±7.45岁(P = 0.969)。病例组中PR和NF2的表达显著低于对照组。孕酮暴露时间越长,PR和NF2的表达越低。PR低表达(OR 11.7;95%CI 4.17 - 32.9;比较PR最低四分位数与最高三个四分位数,P < 0.001)和NF2低表达(OR 4.23;95%CI 1.85 - 9.67;比较NF2最低两个四分位数与最高两个四分位数,P = 0.001)与脑膜瘤风险增加之间也存在显著关联。在本研究中,我们发现外源性孕酮暴露时间越长,血清中PR和NF2 mRNA的表达越低。PR和NF2低表达与脑膜瘤风险较高相关,这表明PR低表达和NF2失活可能在孕酮相关的脑膜瘤肿瘤发生中起关键作用,并且可能是脑膜瘤高风险女性的潜在临床标志物。

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