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芳香化酶和雌激素受体α mRNA表达作为星形细胞瘤患者的预后生物标志物

Aromatase and estrogen receptor alpha mRNA expression as prognostic biomarkers in patients with astrocytomas.

作者信息

Dueñas Jiménez J M, Candanedo Arellano A, Santerre A, Orozco Suárez S, Sandoval Sánchez H, Feria Romero I, López-Elizalde R, Alonso Venegas M, Netel B, de la Torre Valdovinos B, Dueñas Jiménez S H

机构信息

Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico,

出版信息

J Neurooncol. 2014 Sep;119(2):275-84. doi: 10.1007/s11060-014-1509-z. Epub 2014 Jul 9.

Abstract

Estrogens are oncogenic hormones at a high level in breast, prostate, endometrial and lung cancer. Estrogens are synthesized by aromatase which has been used as a biomarker both in breast and lung cancer. Estrogen biological activities are executed by their classic receptors (ERα and ERβ). ERα has been described as a cancer promoter and ERβ, as a possible tumor suppressor. Both receptors are present at low levels in primary multiforme glioblastoma (GBM). The GBM frequency is 50 % higher in men than in women. The GBM patient survival period ranges from 7 to 18 months. The purpose of this pilot study was to evaluate aromatase and estrogen receptor expression, as well as 17ß-estradiol concentration in astrocytoma patients biopsies to obtain a prognosis biomarker for these patients. We analyzed 36 biopsies of astrocytoma patients with a different grade (I-IV) of malignity. Aromatase and estrogen receptor mRNA expression were analyzed by semiquantitative RT-PCR, and the E2 levels, by ELISA. E2 concentration was higher in GBM, compared to grade II or III astrocytomas. The number of cells immunoreactive to aromatase and estrogen receptors decreased as the grade of tumor malignity increased. Aromatase mRNA expression was present in all biopsies, regardless of malignity grade or patient age or gender. The highest expression of aromatase mRNA in GBM patients was associated to the worst survival prognostic (6.28 months). In contrast lowest expression of ERα mRNA in astrocytoma patients had a worst prognosis. In conclusion, aromatase and ERα expression could be used as prognosis biomarkers for astrocytoma patients.

摘要

雌激素在乳腺癌、前列腺癌、子宫内膜癌和肺癌中是高水平的致癌激素。雌激素由芳香化酶合成,芳香化酶已被用作乳腺癌和肺癌的生物标志物。雌激素的生物学活性由其经典受体(ERα和ERβ)执行。ERα被描述为癌症促进因子,而ERβ则可能是肿瘤抑制因子。在原发性多形性胶质母细胞瘤(GBM)中,这两种受体的水平都很低。GBM在男性中的发病率比女性高50%。GBM患者的生存期为7至18个月。这项初步研究的目的是评估星形细胞瘤患者活检组织中芳香化酶和雌激素受体的表达,以及17β-雌二醇的浓度,以获得这些患者的预后生物标志物。我们分析了36例不同恶性程度(I-IV级)的星形细胞瘤患者的活检组织。通过半定量RT-PCR分析芳香化酶和雌激素受体mRNA的表达,通过ELISA分析E2水平。与II级或III级星形细胞瘤相比,GBM中的E2浓度更高。随着肿瘤恶性程度的增加,对芳香化酶和雌激素受体免疫反应的细胞数量减少。无论恶性程度、患者年龄或性别如何,所有活检组织中均存在芳香化酶mRNA表达。GBM患者中芳香化酶mRNA的最高表达与最差的生存预后(6.28个月)相关。相反,星形细胞瘤患者中ERα mRNA的最低表达预后最差。总之,芳香化酶和ERα表达可作为星形细胞瘤患者的预后生物标志物。

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