雄激素受体活性与胶质母细胞瘤患者的生存预后较差相关。

Androgen Receptor Activity Is Associated with Worse Survival in Glioblastoma.

机构信息

Department of Neurosurgery, Hospital Universitario de Canarias, CP 38320 S/C de Tenerife, Spain.

Clinical Neuroscience Research Group, Health Science Campus, University of La Laguna, CP 38320 S/C de Tenerife, Spain.

出版信息

J Integr Neurosci. 2022 Apr 22;21(3):86. doi: 10.31083/j.jin2103086.

DOI:10.31083/j.jin2103086

PMID:35633167

Abstract

BACKGROUND

Some evidence about the role of the androgen receptor (AR) in pathogenesis of glioblastoma have been reported, but no study has focused on measuring the activity of the AR in GB. Therefore, the aim of this work is to study the role of AR and its activity as prognostic biomarkers in glioblastoma (GB).

METHODS

Molecular and clinical data from The Cancer Genome Atlas database were used. The AR-expression at protein-level was obtained from reversed phase protein array (RPPA) assays. The AR-activity was determined by calculating the AR-score, an index calculated by using the expression (at RNA-level) of 13 androgen-responsive-genes. Univariate and multivariate Cox-regression analyses were performed. Finally, a correlation analysis was conducted between protein expression data and the AR-score.

RESULTS

Two-hundred and thirty-three patients were included. RPPA data showed a mean AR abundance of 0.027(Statistical Deviation = 0.38) in GB. The univariate Cox-regression analysis showed that the AR-Score was associated with a worse prognosis (Hazard Ratio (HR) = 1.070) while the AR-expression did not show any relationship with survival (HR = 0.869). The association of the AR-score with worse overall survival (OS) was still significant in the multivariate analysis (HR = 1.054). The highest correlation coefficients between the AR-score and RPPA were identified in a group of proteins involved in apoptotic process regulation.

CONCLUSIONS

GB patients with a high AR-activity present a worse prognosis in terms of OS. Thus, the activity of the AR may have a pathogenic role in GB. In this regard, the activation of the AR in GB may be associated with a dysregulation of apoptosis.

摘要

背景

已有一些关于雄激素受体（AR）在胶质母细胞瘤发病机制中的作用的证据，但尚无研究关注 AR 在 GB 中的活性。因此，本研究旨在探讨 AR 及其作为胶质母细胞瘤（GB）预后生物标志物的活性。

方法

使用来自癌症基因组图谱数据库的分子和临床数据。通过反相蛋白阵列（RPPA）检测获得 AR 蛋白水平的表达。通过计算 AR 评分来确定 AR 活性，该指数是使用 13 种雄激素反应基因的表达（在 RNA 水平上）计算得出的。进行单变量和多变量 Cox 回归分析。最后，进行了蛋白表达数据与 AR 评分之间的相关性分析。

结果

共纳入 233 例患者。RPPA 数据显示，GB 中 AR 丰度的平均值为 0.027（统计偏差=0.38）。单变量 Cox 回归分析表明，AR 评分与预后不良相关（风险比（HR）=1.070），而 AR 表达与生存无任何关系（HR=0.869）。在多变量分析中，AR 评分与总生存期（OS）较差的相关性仍然显著（HR=1.054）。在一组参与凋亡过程调控的蛋白中，鉴定出 AR 评分与 RPPA 之间的最高相关系数。