从高风险肝母细胞瘤到癌瘤的异步过渡
Xinjian Yu1, Stephen Sarabia2, Martin Urbicain2
1Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.
Journal of hepatology
|March 2, 2026
概括
具有癌瘤特征的肝细胞瘤 (HBC) 是复杂的儿科肝脏瘤. 我们的研究表明,它们起源于早期的肝干细胞,具有WNT信号错误,导致不良结果和化学抵抗.
科学领域:
- 儿科瘤学 儿科瘤学
- 肝细胞瘤 肝细胞瘤
- 分子病理学分子病理学
背景情况:
- 儿童肝脏瘤通常是肝细胞母细胞瘤 (HB) 或肝细胞癌 (HCC).
- 一个子集,具有癌症特征的肝细胞瘤 (HBCs),呈现混合的组织学和分子特征,以前称为肝细胞新生瘤-未经指定 (HCN-NOS).
- 细胞组成,生物驱动因素和HBC的进化轨迹仍然不太清楚.
研究的目的:
- 描述具有癌症特征 (HBCs) 的肝细胞母细胞瘤的生物学,病因学,细胞组成和进化动态.
- 研究细胞起源和 HBC 发育和进展背后的分子机制.
- 评估HBC细胞亚型,治疗反应和患者结果之间的关系.
主要方法:
- 多omics分析,包括单核RNA测序 (snRNA-seq) 和单核DNA测序 (snDNA-seq).
- 多区域纵向散装RNA和DNA测序.
- 分析主要是化疗后切除样本 (三分之二).
主要成果:
- 肝细胞由HB型,HB型和HC型分子细胞类型的异质混合物组成.
- 与HB相比,HBC表现出明显较差的结果和更大的化学抵抗,受细胞身份,遗传变化和分化阶段的影响.
- 肝血球是由HB前体产生的,具有异常WNT信号,导致分化停止;WNT抑制增强化疗敏感性.
- 肝细胞表现出动态的进化过渡,从肝细胞转变为肝细胞,从肝细胞转变为肝细胞.
结论:
- 多omics分析显示,HBCs起源于在早期肝干细胞阶段被捕的HB前体.
- 异常的WNT信号对于在HBC中观察到的分化停止至关重要.
- 了解HBC生物学可以了解儿科肝癌异质性和潜在的治疗标.
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