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雄激素受体表达对转移性乳腺癌临床特征的影响。

The effect of androgen receptor expression on clinical characterization of metastatic breast cancer.

作者信息

Kim Ji-Yeon, Park Kyunghee, Lee Eunjin, Jung Hae Hyun, Ahn Jin Seok, Im Young-Hyuck, Park Woong-Yang, Park Yeon Hee

机构信息

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul 06351, Korea.

Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea.

出版信息

Oncotarget. 2017 Jan 31;8(5):8693-8706. doi: 10.18632/oncotarget.14414.

Abstract

In breast cancer (BC), androgen receptor (AR) expression is related to estrogen receptor (ER) and/or progesterone receptor (PgR) expression. AR expression is an indicator of good prognosis in breast cancer regardless of hormone receptor (HR) status. In this study, we evaluated the effect of AR-related gene expression on clinical characterization of metastatic BC. We performed RNA-Seq to evaluate gene expression using mRNA extracted from 37 patients with metastatic BC. Intrinsic subtype prediction, analysis of differential gene expression, and gene set enrichment pathway analysis were then performed. Metastatic BCs were categorized into three subgroups based on AR, ER, PgR, and HER2 expression. According to this subcategorization, 70 genes including AR, ER, and HER2 were differentially expressed among the three groups. In gene set enrichment pathway analysis, the low AR group was associated with the cell cycle pathway, whereas mammalian target of rapamycin (mTOR) pathways was prevalent in the high ER and AR group. In survival analysis, a higher level of AR expression correlated with prolonged overall survival in metastatic BC (high expression vs. low expression, median OS 53.1 vs. 27.2 months, p=.001). In conclusion, we propose that AR and AR-related gene expression could be utilized to predict the prognosis of metastatic BC and thus may be useful in treatment planning for refractory BC.

摘要

在乳腺癌(BC)中,雄激素受体(AR)表达与雌激素受体(ER)和/或孕激素受体(PgR)表达相关。无论激素受体(HR)状态如何,AR表达都是乳腺癌预后良好的一个指标。在本研究中,我们评估了AR相关基因表达对转移性BC临床特征的影响。我们进行了RNA测序,以使用从37例转移性BC患者中提取的mRNA评估基因表达。然后进行内在亚型预测、差异基因表达分析和基因集富集途径分析。转移性BC根据AR、ER、PgR和HER2表达分为三个亚组。根据这种亚分类,包括AR、ER和HER2在内的70个基因在三组之间差异表达。在基因集富集途径分析中,低AR组与细胞周期途径相关,而哺乳动物雷帕霉素靶蛋白(mTOR)途径在高ER和AR组中普遍存在。在生存分析中,AR表达水平较高与转移性BC的总生存期延长相关(高表达与低表达,中位总生存期分别为53.1个月和27.2个月,p = 0.001)。总之,我们提出AR和AR相关基因表达可用于预测转移性BC的预后,因此可能有助于难治性BC的治疗规划。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c823/5352433/d4ffb3acf4b9/oncotarget-08-8693-g001.jpg

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