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多焦肝细胞癌中的基因组和瘤微环境异质性

Yongheng Yang¹, Qingqiang Ni², Hongguang Li²

¹Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Hepatology (Baltimore, Md.)

|August 20, 2025

概括

肝癌中的肝内转移 (IM) 和多中心发生 (MO) 具有不同的瘤微环境 (TME). 与MO相比,IM瘤呈现出更大的异质性和免疫细胞特征的改变,影响了预后.

科学领域:

癌症学
免疫学
基因组学

背景情况:

多焦点肝细胞癌 (HCC) 由于瘤微环境 (TME) 的模两可,因此存在诊断和治疗方面的挑战.
区分肝脏内转移 (IM) 和多中心发生 (MO) 对于理解HCC异质性至关重要.

研究的目的:

在多焦性HCC中描述和比较IM和MO的TME.
确定区分IM和MOTME的细胞和分子特征.
在多焦性HCC中探索特定免疫细胞群的预后意义.

主要方法:

在7名HCC患者的23个样本上进行了并行全外体测序和单细胞RNA测序 (scRNA-seq).
在额外的患者队列中进行免疫组织化学验证.
对基因组和转录组数据进行综合分析,以分析TME.

主要成果:

在IM中,恶性细胞表现出比MO更高的瘤内异质性,干性和代谢激活.
IM瘤具有相似的TME,而MO瘤具有不同的TME.
与MO相比,IM显示CD20+B细胞,血细胞和cDC2s的减少,T细胞的终极耗尽较多.
在多焦性HCC中,CD20和CD1C表达与更好的预后相关.
丰富了MMP9+巨细胞,形成了具有调节性T细胞和耗尽的T细胞的.

结论:

这项研究阐明了多焦性HCC中IM和MO之间的异质TME.
这些发现提供了多焦点HCC的全面景观,有助于诊断和治疗策略.

关键词:

B 单元格树突细胞耗尽的T细胞一个单元与瘤相关的巨细胞

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