摘要

  雄激素受体 (AR) 表达的作用及其在肝细胞癌 (HCC) 预后中的活性仍无定论。本研究的目的是分析 AR 表达及其作为 HCC 预后生物标志物的活性的作用。包括来自癌症基因组图谱 (TCGA) 的 337 名患者（107 名女性；59.42 岁 [SD = 13.0]）。为了推断 AR 活性，包括了先前验证的雄激素反应基因 (ARG) 的表达谱。 AR 活性由基于所选 ARG 的表达计算的 AR-Score-21（21 个 ARG）和 AR-Score-13（13 个 ARG）显示。那些在组织学等级之间表达显着不同的 ARG 被用于计算两个新的 AR 分数。具有较高 AR 表达的 HCC 患者显示出较高的中位总生存期 (OS)。 AR-Score 21 和 AR-Score-13 与预后没有任何关联。 AR-Score-21 的 21 个 ARG 中的 6 个和 AR-Score-13 的 13 个 ARG 中的 7 个在组织学级别之间显示出显着不同的表达谱。基于这些差异，计算了另外两个 AR-Scores（AR-Score-6 和 AR-Score-7）。他们显示在高级别 HCC 中上调到下调的 ARG 相对增加。由这些 AR 分数推断出的较高 AR 活动与较差的结果相关。 AR的表达与HCC更好的预后相关。然而，AR 的活性似乎在组织学等级之间存在质的差异。由移动的 ARG 推断的 AR 活性与 HCC 患者的较差预后相关。

  The role of the Androgen Receptor (AR) expression and its activity in the prognosis of hepatocellular carcinoma (HCC) remains inconclusive. The aim of this study is to analyze the role of the AR expression and its activity as prognostic biomarkers in HCC. Three-hundred and thirty-seven patients from The Cancer Genome Atlas (TCGA) (107 females; 59.42 years [SD = 13.0]) were included. To infer AR activity, the expression-profile of previously validated androgen responsive genes (ARGs) was included. AR activity was shown by the AR-Score-21 (21 ARGs) and AR-Score-13 (13 ARGs) that were computed based on the expression of the selected ARGs. Those ARGs whose expression was significantly different between histological grades were used for computing two new AR-Scores. HCC patients with higher AR expression showed a higher median overall survival (OS). AR-Score 21 and AR-Score-13 did not show any association with prognosis. Six of the 21 ARGs of the AR-Score-21 and 7 of the 13 ARGs of the AR-Score-13 showed a significant different expression profile among histological grades. Based on these differences, another two AR-Scores were computed (AR-Score-6 and AR-Score-7). They showed the relative increase of upregulated to downregulated ARGs in high-grade HCC. Higher AR activity inferred by these AR-Scores was associated with worse outcomes. The expression of AR is associated with a better prognosis in HCC. However, the activity of the AR seems to be qualitatively different among histological grades. The AR activity inferred by the shifted ARGs is associated with a worse prognosis in HCC patients.

  https://www.nature.com/articles/s41598-020-79177-2