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基于DNA甲基化数据的炎症性乳腺癌微环境谱的解卷揭示了可操作的目标,以提高治疗疗效
Naiade Calanca1,2, Flavia Lima Costa Faldoni1, Cristiano Pádua Souza3
1Department of Clinical Genetics, University Hospital of Southern Denmark, Beriderbakken 4, Vejle, DK, 7100, Denmark.
Journal of translational medicine
|August 5, 2024
概括
炎症性乳腺癌 (IBC) 具有独特的瘤微环境 (TME) 细胞组成. 在IBC中,更高的内皮细胞和树皮细胞透率与更好的生存率相关,并表明了新的治疗点.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 炎症性乳腺癌 (IBC) 与急性炎症具有相同的临床症状,但其瘤微环境 (TME) 细胞组成和表观遗传变化在很大程度上仍未被描述.
- TME的分子变化,包括表皮移除,在形态异常之前发生,并影响癌症的预后和治疗反应.
- 了解IBC TME内的免疫和 stromal 细胞的相互作用对于开发有效的治疗方法至关重要.
研究的目的:
- 为了研究IBC和周围组织的全球DNA甲基化概况.
- 在IBC中估计TME细胞组成.
- 确定与IBC预后和潜在治疗点相关的表观遗传失调标记.
主要方法:
- 利用HiTIMED算法将IBC和周围非瘤组织 (SNT) 的DNA甲基化数据解,以确定细胞组成.
- 评估了透细胞类型的预后相关性及其与临床病理学变量之间的相关性.
- 在独立的IBC和非IBC队列中对CD34 (内皮细胞标记物) 和CD68 (巨细胞标记物) 进行了免疫光染色.
主要成果:
- 与SNT样本相比,IBC样本显示内皮细胞,树皮细胞,记忆B细胞,树突细胞和自然杀手细胞的透率较低.
- 较高的内皮细胞 (EC) 和树皮细胞比例与IBC患者的整体存活率的改善有关.
- 在IBC和SNT之间观察到不同的DNA甲基化概况,CD40,CD34和EMCN等基因的高甲基化;在IBC中发现显著更高的CD34和CD68蛋白质表达.
结论:
- 在IBC TME中确定了与更好的患者存活相关的特定细胞子集.
- 在IBC中突出显示失调的表观遗传标记 (例如CD34,CD68).
- 建议免疫疗法和表观遗传药物的组合可以针对这些已识别的标记物,以改善IBC治疗结果.
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