乳腺癌中葡萄糖皮质体受体异型对个性化支持疗法产生影响
Henriett Butz1,2,3,4, Viktória Vereczki1,5, Barna Budai1
1Department of Molecular Genetics, The National Tumour Biology Laboratory, Comprehensive Cancer Centre, National Institute of Oncology, 1122 Budapest, Hungary.
International journal of molecular sciences
|November 9, 2024
概括
细胞质中的葡萄糖皮质体受体β (GRβ) 与三阴性乳腺癌 (TNBC) 的更好的存活率有关. 核GR总染色可能表明这些患者的风险更高,存活时间更短.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- 葡萄糖皮质体受体 (GR) 激活与转移有关,特别是雌激素受体阴性和三阴性乳腺癌 (TNBC).
- 具有与原始GR异型相反的作用的GRβ异型在临床乳腺癌样本中以前没有被研究过.
研究的目的:
- 分析乳腺癌细胞中总GR和GRβ的细胞内定位.
- 为了比较乳腺癌不同分子亚型的GR和GRβ表达.
- 为了研究GR表达/局部化和TNBC患者的生存结果之间的关联.
主要方法:
- 使用等离子体构造和光免疫细胞化学用于GR和GRβ定位的体外分析.
- 针对总GR和GRβ表达的194个临床乳腺癌样本的免疫结合.
- 161个TNBC样本的免疫染和对1097个TNBC病例的RNA数据进行分析,以求生存相关性.
主要成果:
- 在连接体激活后,GR从细胞质转移到细胞核.
- 细胞质GRtotal在光线A瘤中与Ki67呈负相关性,但在TNBC中呈正相关性.
- 高核GR总染色与较短的无进展生存相关,而高细胞质GRβ与TNBC中更好的整体生存相关.
结论:
- 这项研究是首次报告乳腺瘤中的GRβ表达,揭示了GRtotal和GRβ在分子亚型中的独特局部化和表达模式.
- 细胞质GR总和光线A和TNBC中的Ki67增殖指数之间存在反向关联.
- 细胞质GRβ表明TNBC的预后更好,而核GR总染色可能预测疾病进展的风险更高,生存率更差.
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