转移是结直肠癌（CRC）患者死亡的主要原因。探索转移机制对于结直肠癌的临床和基础研究都具有重要意义。结直肠癌是一种高度异质性的疾病，其治疗结果存在差异。在这项研究中，我们应用空间转录组学（ST）从两个原发性结直肠癌组织及其匹配的肝转移组织中生成组织范围的转录组。空间 RNA 信息显示原发组织和转移组织的瘤内异质性 (ITH)。跨组织基因表达的比较揭示了转移组织中癌症干细胞（CSC）的明显富集，并将 FOXD1 确定为一种新的转移性 CSC 标志物。轨迹和伪时间分析揭示了转移过程中不同的进化轨迹和去分化-分化过程。 CellphoneDB 分析表明 CD74-MIF 与转移组织中的肿瘤细胞相互作用占主导地位。进一步的分析证实 FOXD1 是 CSC 的标志物和患者生存率的预测因子，尤其是在转移性疾病中。我们的研究发现了原发组织和转移组织的 ITH，为 CRC 肝转移的细胞机制提供了新的见解，并为 CRC 转移的治疗策略奠定了基础。版权所有 © 2024。由 Elsevier B.V. 出版。

Metastasis is the main cause of mortality in colorectal cancer (CRC) patients. Exploring the mechanisms of metastasis is of great importance in both clinical and fundamental CRC research. CRC is a highly heterogeneous disease with variable therapeutic outcomes of treatment. In this study, we applied spatial transcriptomics (ST) to generate a tissue-wide transcriptome from two primary colorectal cancer tissues and their matched liver metastatic tissues. Spatial RNA information showed intratumoral heterogeneity (ITH) of both primary and metastatic tissues. The comparison of gene expressions across tissues revealed an apparent enrichment of cancer stem cells (CSCs) in metastatic tissues and identified FOXD1 as a novel metastatic CSC marker. Trajectory and pseudo-time analyses revealed distinct evolutionary trajectories and a dedifferentiation-differentiation process during metastasis. CellphoneDB analysis suggested a dominant interaction of CD74-MIF with tumor cells in metastatic tissues. Further analysis confirmed FOXD1 as a maker of CSCs and the predictor of patient survival, especially in metastatic diseases. Our study found ITH of primary and metastatic tissues and provides novel insights into the cellular mechanisms underlying liver metastasis of CRC and foundations for therapeutic strategies for CRC metastasis.Copyright © 2024. Published by Elsevier B.V.