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在肝细胞癌中,瘤内表观遗传异质性和异常分子钟

Paula Restrepo^1,2,3,4, Adrian Bubie¹, Amanda J Craig⁵

¹Departments of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029.

medRxiv : the preprint server for health sciences

|November 24, 2025

概括

表观遗传变化驱动肝细胞癌 (HCC) 的瘤进化. 这项研究揭示了一种新的甲基化驱动的瘤内异质性 (mITH) 轴,以及与瘤适应性和HCC的免疫反应相关的表观遗传衰老指标.

科学领域:

表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
在瘤学瘤学.
基因组学就是基因组学.

背景情况:

对肝细胞癌 (HCC) 瘤演变中的表观遗传驱动因素的有限理解.
瘤内异质性 (ITH) 是HCC进展和治疗耐药性的关键因素.

研究的目的:

描述DNA甲基化对早期HCC瘤内异质性 (mITH) 的表观遗传贡献.
确定与瘤演变,健康状况和临床结果相关的新型表观遗传标记.

主要方法:

在47个未经治疗的HCC活检中利用区域增强的减少表示双硫酸盐测序 (RE-RRBS).
综合DNA甲基化数据与RNA测序,向DNA测序,瘤透淋巴细胞 (TIL) 和B型肝炎病毒表达数据.
使用TCGA-LIHC队列数据 (377名患者) 分析了表观遗传瘤年龄和临床结果.

主要成果:

在44%的HCC患者中,在促进体和增强体区域中确定了大量的mITH特征,仅通过RNA分析无法检测到.
开发了一种表观遗传瘤衰老测量方法,反映了瘤的适应性和潜在的克隆性.
发现表观遗传上"较老"的HCC瘤表现出较低的健康状况,但较高的TIL负担.

结论:

揭示了一种由DNA甲基化驱动的HCC中ITH的新型表观遗传轴.
表观遗传年龄作为瘤适应性和免疫透的潜在代理.
这些发现为HCC病原体和潜在的治疗点提供了新的见解.

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