大肠癌(CRC)患者长期预后的主要因素之一是远处转移。然而，CRC转移的驱动因素在单个细胞水平上尚未明确，这限制了对准确预测和预防CRC转移的深入研究，以改善预后。本研究通过单细胞RNA(scRNA)测序数据，研究了转移和非转移CRC肿瘤微环境(TME)之间的异质性，详细分析了来自20份主要CRC样本的50,462个单细胞，其中包括40,910个来自非转移CRC(M0组)和9552个来自转移CRC(M1组)。基于单细胞图谱，我们揭示了相对较高比例的癌细胞和成纤维细胞在转移性CRC中相较于非转移性CRC。此外，还确定了在转移性CRC中的两个特定的癌细胞亚型（FGGY+SLC6A6+和IGFBP3+KLK7+癌细胞）和三个特定的成纤维细胞亚型（ADAMTS6+CAPG+、PIM1+SGK1+和CA9+UPP1+成纤维细胞）。通过富集和轨迹分析，阐明了这些特定细胞亚群的功能和分化特征。这些结果为未来深入研究筛选有效的方法和药物以预测和预防CRC转移来改善预后提供了基本知识。版权所有©2023 Elsevier Inc.发布。

One of the main factors hampering the long-term prognosis of colorectal cancer (CRC) patients is distant metastasis. However, the driving factors of CRC metastasis have not been clarified at the single-cell level, which limits the in-depth study of accurate prediction and prevention of CRC metastasis to improve the prognosis.Heterogeneities in the tumor microenvironment (TME) between metastatic and nonmetastatic CRC were investigated by single-cell RNA (scRNA) sequencing data. In detail, 50,462 single cells from 20 primary CRC samples, including 40,910 cells from nonmetastatic CRC (M0 group) and 9552 cells from metastatic CRC (M1 group), were systematically analyzed in this study.Based on the single-cell atlas, we revealed that cancer cells and fibroblasts accounted for relatively high proportions in metastatic CRC compared with nonmetastatic CRC. Moreover, two specific cancer cell subtypes (FGGY+SLC6A6+ and IGFBP3+KLK7+ cancer cells) and three specific fibroblast subtypes (ADAMTS6+CAPG+, PIM1+SGK1+ and CA9+UPP1+ fibroblasts) in metastatic CRC were identified. The functional and differentiation characteristics of these specific cell subclusters were elucidated by enrichment and trajectory analyses.These results provide fundamental knowledge for future in-depth research to screen effective methods and drugs to predict and prevent CRC metastasis to improve prognosis.Copyright © 2023. Published by Elsevier Inc.