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多焦点肝细胞癌中的肝内微生物异质性及其与宿主基因组和转录基因组改变的关联

Yinghong Lu¹, Lixia Xu², Weikang Chen²

¹Chinese University of Hong Kong, Hong Kong, Hong Kong.

Cancer discovery

|April 27, 2025

概括

肝脏内微生物组在多焦点肝细胞癌 (HCC) 类型之间有所不同,特定的细菌与瘤进展和转移有关. 细菌生物标记面板可以区分这些HCC亚型.

科学领域:

微生物学微生物学
在瘤学瘤学.
基因组学就是基因组学.

背景情况:

肝脏内微生物组在多焦点肝细胞癌 (HCC) 中的作用及其与基因组变化的联系尚不清楚.
多焦点HCC由于其异质性质,提出了复杂的挑战.

研究的目的:

为了研究多焦点HCC.的肝脏内微生物群签名.
探索微生物群落与基因组改变之间的关联.
要区分肝脏内转移 (IM) -HCC和多中心发生 (MO) -HCC.

主要方法:

在242个HCC瘤结节和58个邻近的非瘤组织中进行了多种OMIC分析.
通过格拉姆染色,LPS,LTA染色和传输电子显微镜 (TEM) 确认细菌的存在.
突变剖析用于分层患者并分析细菌社区差异.

主要成果:

在多焦点HCC中发现了异构的微生物群落.
在IM-HCC和MO-HCC结节之间,细菌群落显著不同 (P=0.01).
一个9种细菌的生物标志物小组在区分IM和MO结节时获得了0.795的AUROC.
皮质-介质细胞过渡 (EMT) 在IM结节中升高调节,与特定细菌相关 (例如,Enterococcus faecalis,Streptococcus anginosus).
富含IM的细菌通过诱导免疫抑制微环境和EMT在小鼠模型中促进了HCC细胞迁移,入侵和瘤进展.

结论:

肝脏内微生物组对多焦点HCC的异质性和病原性有显著的贡献.
特定的细菌物种与不同的HCC亚型相关,并通过EMT和免疫调节驱动瘤进展.
鉴定到的细菌生物标记面板显示了区分HCC亚型的潜力.

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