小柯机器人

近日，复旦大学樊嘉等研究人员合作发现，综合多组学分析分析转移性肝细胞癌的时空演变。相关论文于2023年12月14日在线发表在《癌细胞》杂志上。

研究人员对来自182名肝细胞癌（HCC）患者的257个原发区域和176个转移区域进行了多组学分析。富含缺氧特征的原发肿瘤有利于多克隆传播。原发性和转移性HCC之间的基因组差异很大，而且普遍存在早期传播。在转移瘤中观察到的明显的新抗原瘤内异质性与T细胞反应性降低有关，而T细胞反应性降低的原因是新抗原表达紊乱。研究人员发现体细胞拷贝数改变是导致转移的高选择性事件。

与有Wnt突变的亚克隆相比，没有Wnt突变的亚克隆显示出更强的转移选择优势，其特点是微环境中富含活化的成纤维细胞，有利于转移表型的形成。最后，无Wnt突变的转移灶表现出更高的免疫抑制B细胞富集，这些B细胞通过HLA-E:CD94-NKG2A检查点轴介导CD8⁺ T细胞的终末耗竭。总之，这些研究结果从多维度剖析了转移的复杂演变过程。

据了解，目前还缺乏对转移性HCC的全面分子分析。

附：英文原文

Title: Integrated multi-omics profiling to dissect the spatiotemporal evolution of metastatic hepatocellular carcinoma

Author: Yunfan Sun, Pin Wu, Zefan Zhang, Zejian Wang, Kaiqian Zhou, Minfang Song, Yuan Ji, Fenglin Zang, Limu Lou, Keqiang Rao, Pengxiang Wang, Yutong Gu, Jie Gu, Binbin Lu, Limeng Chen, Xiuqi Pan, Xiaojing Zhao, Lihua Peng, Dongbing Liu, Xiaofang Chen, Kui Wu, Penghui Lin, Liang Wu, Yulin Su, Min Du, Yingyong Hou, Xinrong Yang, Shuangjian Qiu, Yinghong Shi, Huichuan Sun, Jian Zhou, Xingxu Huang, David H. Peng, Liye Zhang, Jia Fan

Issue&Volume: 2023-12-14

Abstract: Comprehensive molecular analyses of metastatic hepatocellular carcinoma (HCC) arelacking. Here, we generate multi-omic profiling of 257 primary and 176 metastaticregions from 182 HCC patients. Primary tumors rich in hypoxia signatures facilitatedpolyclonal dissemination. Genomic divergence between primary and metastatic HCC ishigh, and early dissemination is prevalent. The remarkable neoantigen intratumor heterogeneityobserved in metastases is associated with decreased T cell reactivity, resulting fromdisruptions to neoantigen presentation. We identify somatic copy number alterationsas highly selected events driving metastasis. Subclones without Wnt mutations showa stronger selective advantage for metastasis than those with Wnt mutations and arecharacterized by a microenvironment rich in activated fibroblasts favoring a pro-metastaticphenotype. Finally, metastases without Wnt mutations exhibit higher enrichment ofimmunosuppressive B cells that mediate terminal exhaustion of CD8+ T cells via HLA-E:CD94-NKG2A checkpoint axis. Collectively, our results provide amulti-dimensional dissection of the complex evolutionary process of metastasis.

DOI: 10.1016/j.ccell.2023.11.010

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00401-4

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
官方网址：https://www.cell.com/cancer-cell/home
投稿链接：https://www.editorialmanager.com/cancer-cell/default.aspx