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Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
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Single-Cell Transcriptomic Landscape of Right-Sided Colon Cancer Reveals Cellular and Molecular Features of
Zhixin Ye1, Wanrui Zhang2, Hongshen Qiu2
1Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Biomedicines
|March 28, 2026
Summary
Right-sided colon cancer (RCC) with liver metastasis shows increased genomic instability and stem-like tumor cells. These tumors exhibit metabolic plasticity and microenvironmental changes, revealing key mechanisms of RCC progression.
Area of Science:
- Oncology
- Genomics
- Cell Biology
Background:
- Right-sided colon cancer (RCC) is aggressive and metastasizes to the liver.
- The cellular mechanisms driving RCC liver metastasis are not well understood.
Purpose of the Study:
- To analyze the single-cell RNA sequencing data of primary RCC tumors.
- To compare tumors with and without liver metastasis (RCC_LM vs. RCC_noM).
Main Methods:
- Integrated single-cell RNA sequencing data from eight RCC patients.
- Identified malignant cells using copy number variation inference.
- Compared tumor subclusters, gene expression, pathways, metabolism, and pseudotime between RCC_LM and RCC_noM.
Main Results:
- RCC_LM tumors showed higher genomic instability and G1 phase cell cycle progression.
- Stem-like tumor cells were enriched in RCC_LM, while enterocyte-like cells predominated in RCC_noM.
- Metastatic tumors displayed signatures of epithelial-mesenchymal transition, ECM remodeling, inflammation, and metabolic reprogramming (glycolysis, oxidative phosphorylation).
Conclusions:
- Liver metastatic potential in RCC is associated with stem-like tumor states.
- Metabolic plasticity and microenvironmental remodeling are critical in RCC progression.
- These findings offer insights into the cellular basis of RCC liver metastasis.
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