Department of Radiation Oncology, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198-7521, USA.
School of Biological Sciences, University of Nebraska - Lincoln, Lincoln, NE, USA.
Sci Rep. 2024 Sep 27;14(1):22122. doi: 10.1038/s41598-024-72284-4.
Androgen receptor (AR) overexpression has been identified in gliomas and its stem cells, suggesting that AR plays an important role in tumor carcinogenesis. The prognostic significance of AR overexpression in gliomas remains unknown. AR mRNA expression in gliomas and relevant clinical data were obtained from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. AR expression levels were compared across gliomas of different histopathologic grades and molecular subtypes. Kaplan-Meier analyses in patients with different AR expression levels were investigated for the potential prognostic values of AR. Compared with normal brain tissue, gliomas show significantly higher AR mRNA expression (p < 0.01). AR mRNA expression was more prominent in higher grade disease and in worse prognostic molecular subtypes (p < 0.01). AR protein is more abundant in glioblastoma than in lower grade gliomas (LGG) (grade 2/3) (p < 0.0001). This is corroborated by a linear association between AR mRNA and protein expression (r = 0.65). In LGG, both higher AR mRNA and protein expression was associated with significantly worse overall survival (OS). Five-year OS for LGG patients with high versus low AR expression were 59.1% and 73.3%, respectively (p < 0.0001). AR expression is not prognostic for OS within glioblastoma patients. Gender was not associated with AR expression or prognosis. Higher AR expression levels are associated with higher grade disease and histopathologic features predicting poorer prognosis in lower grade gliomas. Higher gene expression in LGG patients is correlated with poor prognosis but not in the glioblastoma cohort suggesting saturated expression/functions of AR in glioblastoma.
雄激素受体 (AR) 在神经胶质瘤及其干细胞中过表达，表明 AR 在肿瘤发生中发挥重要作用。AR 过表达在神经胶质瘤中的预后意义尚不清楚。从癌症基因组图谱和中国神经胶质瘤基因组图谱数据库中获得了 AR 在神经胶质瘤中的 mRNA 表达和相关临床数据。比较了不同组织病理学分级和分子亚型的神经胶质瘤中的 AR 表达水平。对不同 AR 表达水平的患者进行 Kaplan-Meier 分析，以研究 AR 的潜在预后价值。与正常脑组织相比，神经胶质瘤显示出明显更高的 AR mRNA 表达（p<0.01）。AR mRNA 表达在高级别疾病和预后较差的分子亚型中更为明显（p<0.01）。与低级别神经胶质瘤（LGG）（分级 2/3）相比，胶质母细胞瘤中 AR 蛋白更为丰富（p<0.0001）。这与 AR mRNA 和蛋白表达之间的线性关联一致（r=0.65）。在 LGG 中，较高的 AR mRNA 和蛋白表达均与总生存期（OS）显著降低相关。高 AR 表达的 LGG 患者的 5 年 OS 为 59.1%，低 AR 表达的患者为 73.3%（p<0.0001）。AR 表达对胶质母细胞瘤患者的 OS 无预后意义。性别与 AR 表达或预后无关。在低级别神经胶质瘤中，较高的 AR 表达水平与较高的疾病分级和预测预后较差的组织病理学特征相关。LGG 患者的高基因表达与预后不良相关，但在胶质母细胞瘤队列中则不然，这表明 AR 在胶质母细胞瘤中表达/功能已饱和。
