Single-cell RNA-seq analysis of cancer-endothelial cell interactions in primary tumor and peritoneal metastasis from a single patient with colorectal cancer

Abstract Background Peritoneal metastasis, a major complication of colorectal cancer (CRC), often leads to poor quality of life and unfavorable outcomes. Despite numerous studies characterizing its biological features in CRC, intratumor heterogeneity and interactions between cancer cells and tumor microenvironment cells remain poorly understood. Methods To explore these aspects, we performed single-cell transcriptome analysis of matched primary tumor and peritoneal metastasis samples from a treatment-naïve patient. Results Our analysis revealed enrichment of “tip” endothelial cells in the primary tumor, driving angiogenic sprouting, whereas these cells were absent in peritoneal metastases. Moreover, cancer cells in peritoneal metastasis displayed a distinct expression signature associated with epithelial–mesenchymal transition and tumor invasiveness. Analysis of cell–cell communication between endothelial and tumor cells revealed decreased VEGF signaling and increased CXCL–ACKR1 interactions in peritoneal metastasis. Conclusions Although limited by its N-of-1 design and requiring further validation, our study provides preliminary observations suggesting that alterations in cancer-endothelial cell interactions could reduce dependence on VEGF signaling and influence immune cell infiltration in CRC peritoneal metastasis.