复旦大学陈飞团队近日取得一项新成果。经过不懈努力，他们的论文发现了配对患者来源的类器官揭示了乳腺癌转移中转录因子驱动的表观遗传重塑。该研究于2026年3月16日发表于国际一流学术期刊《细胞—干细胞》杂志上。

研究组建立了一个综合的来自匹配原发肿瘤、邻近正常组织和淋巴结转移的患者来源的类器官（PDOs）生物库。综合基因组学、转录组学和表观遗传学分析表明，这些PDOs保留了肿瘤特异性分子特征，并在疾病进化过程中再现了表观遗传学重塑。表观遗传图谱定义了它们不同的细胞，其特征是独特的转录因子（TF）网络、途径活性和治疗脆弱性，这些都不是传统分类所能完全代表的。淋巴结转移细胞主要由转移性PDOs组成，在转移富集的TFs驱动下表现出广泛的染色质重塑，TFs的缺失明显损害了体内的自发转移。总之，这些发现建立了基于PDO的表观遗传学表征作为阐明乳腺癌进展的调控机制和推进精确治疗策略的平台。

据了解，乳腺癌在肿瘤进展过程中表现出明显的临床异质性和动态的表观遗传重编程，但目前的亚型方法未能捕捉到与转移相关的分子变化。

附：英文原文

Title: Paired patient-derived organoids reveal transcription factor-driven epigenetic remodeling in breast cancer metastasis

Author: Xinxin Rao, Jingwen Wang, Zhibin Qiao, Lei Hong, Mengxue Qiao, Liangwei Ni, Aixia Song, Yun Deng, Xu Zhao, Jin Meng, Xingxing Chen, Yifan Zhou, Jingyan Xue, Yayun Chi, Xinrui Wang, Zhaowei Yu, Qianqian Chen, Congling Xu, Shuang Tang, Jing Hu, Midie Xu, Wei Xu, Zhen Zhang, Yong Zhang, Yanhui Xu, Yi-Zhou Jiang, Jiong Wu, Minhong Shen, Xiaomao Guo, Xiaoli Yu, Fei Xavier Chen

Issue&Volume: 2026-03-16

Abstract: Breast cancer exhibits marked clinical heterogeneity and dynamic epigenetic reprogramming during tumor progression, yet current subtyping approaches fail to capture molecular changes associated with metastasis. Here, we establish a comprehensive biobank of patient-derived organoids (PDOs) from matched primary tumors, adjacent normal tissues, and lymph node metastases. Integrated genomic, transcriptomic, and epigenetic analyses demonstrate that these PDOs preserve tumor-specific molecular signatures and recapitulate epigenetic remodeling during disease evolution. Epigenetic profiling defines four distinct clusters, characterized by unique transcription factor (TF) networks, pathway activities, and therapeutic vulnerabilities not fully represented by conventional classifications. The lymph node metastasis cluster, predominantly comprising metastatic PDOs, displays extensive chromatin remodeling driven by metastasis-enriched TFs, whose depletion markedly impairs spontaneous metastasis in vivo. Together, these findings establish PDO-based epigenetic characterization as a platform for elucidating regulatory mechanisms underlying breast cancer progression and for advancing precision therapeutic strategies.

DOI: 10.1016/j.stem.2026.02.007

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(26)00077-9