Background: Right-sided colon cancer (RCC) is clinically aggressive and prone to liver metastasis, yet the cellular basis underlying its metastatic potential remains unclear. This study aimed to delineate the single-cell landscape of primary RCC tumors with and without liver metastasis. Methods: Public single-cell RNA sequencing datasets of primary right-sided colon tumors from eight patients (five with liver metastasis and three without metastasis) were integrated and analyzed. Malignant cells were identified by copy number variation inference. Tumor subclusters, differential gene expression, pathway enrichment, metabolic activity, and pseudotime trajectories were systematically compared between RCC with liver metastasis (RCCLM) and without metastasis (RCCₙoM). Results: RCCLM tumors exhibited higher genomic instability and a significantly higher proportion of cells in G1 phase, suggesting that altered cell cycle progression is a key feature of tumors with metastatic potential. Five tumor subclusters were identified, with stem-like tumor cells significantly enriched in RCCLM, whereas enterocyte-like cells predominated in RCCₙoM. The primary tumor samples from tumors that metastasized displayed transcriptional programs indicative of epithelial–mesenchymal transition, extracellular matrix remodeling, inflammatory signaling, and metabolic reprogramming involving glycolysis and oxidative phosphorylation. Trajectory analyses indicated that RCCLM tumors were enriched in early pseudotime states, suggesting increased cellular plasticity. Conclusions: These findings indicate that liver metastatic potential in RCC is marked by stem-like tumor states, metabolic plasticity, and microenvironmental remodeling, providing insight into the cellular mechanisms underlying RCC progression.
Ye et al. (Sat,) studied this question.