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

Aromatase and estrogen receptor alpha mRNA expression as prognostic biomarkers in patients with astrocytomas
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DOI:
10.1007/s11060-014-1509-z
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发表时间:
2014-09-01
影响因子:
3.9
通讯作者:
Duenas Jimenez, S. H.
Duenas Jimenez, S. H.
中科院分区:
医学2区
文献类型:
--
作者:
Duenas Jimenez, J. M.;Candanedo Arellano, A.;Duenas Jimenez, S. H.

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雌激素是一种致癌激素,在乳腺癌、前列腺癌、子宫内膜癌和肺癌中含量很高。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。雌激素的生物活性是由其经典受体(ER α和ER β)执行的。ER α被描述为癌症促进剂,ER β被描述为可能的肿瘤抑制剂。这两种受体在原发性多形性胶质母细胞瘤(GBM)中均以低水平存在。男性GBM发生率比女性高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17-雌二醇浓度,以获得这些患者的预后生物标志物。我们分析了36例不同级别(I-IV)恶性星形细胞瘤患者的活检。芳香化酶和雌激素受体mRNA的表达通过半定量RT-PCR分析,E2水平通过ELISA分析。与II级或III级星形细胞瘤相比,GBM中的E2浓度较高。芳香化酶和雌激素受体阳性细胞数随肿瘤恶性程度的增加而减少。芳香化酶mRNA的表达存在于所有活检,无论恶性程度或患者的年龄或性别。GBM患者芳香化酶mRNA表达最高与最差的生存预后(6.28个月)相关。星形细胞瘤ER α mRNA表达水平越低,预后越差.总之,芳香化酶和ER α表达可作为星形细胞瘤患者预后的生物标志物。
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 (ER alpha and ER beta). ER alpha has been described as a cancer promoter and ER beta, 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 17-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 ER alpha mRNA in astrocytoma patients had a worst prognosis. In conclusion, aromatase and ER alpha expression could be used as prognosis biomarkers for astrocytoma patients.