Combining AI to reveal CCDC3-mediated pathways of colorectal cancer liver metastasis - PubMed
5 days ago
- #chromosomal instability
- #colorectal cancer
- #liver metastasis
- Chromosomal instability (CIN) is a critical hallmark in colorectal cancer liver metastases, linked to tumor aggressiveness and poor prognosis.
- The study integrated single-cell RNA sequencing, weighted gene co-expression network analysis, and non-negative matrix factorization to construct a CIN index.
- CIN-high tumor cells exhibit aggressive phenotypes and reside in an immune-excluded tumor microenvironment.
- Cancer-associated fibroblasts (CAFs) showed enhanced communication with CIN-high tumor cells.
- CCDC3, a key CAF-derived gene, was validated to promote metastasis, proliferation, and CIN in vitro and in vivo.
- AI-based bio-knowledge graph analysis revealed CCDC3's core role in chromosomal instability and liver metastasis.
- Mechanistically, CCDC3 interacts with CXCR3 on CRC cells, activating STAT3 phosphorylation and CDT1 transcription.
- Disruption of the CCDC3/CXCR3/STAT3/CDT1 axis suppressed metastatic traits, tumor growth, and liver colonization in mouse models.
- High CCDC3 expression correlated with elevated CIN signatures and worse patient survival.
- The findings highlight CCDC3 as a potential therapeutic target for aggressive, CIN-high colorectal cancer.