Objective:

To characterize fibroblast-associated transcriptional programs in colorectal cancer (CRC) and identify candidate genes with potential biological relevance, which may inform therapeutic strategies.

Approach:

Key Findings:

• Identified 17 cell clusters corresponding to 10 major cell lineages in CRC and adjacent normal tissues, highlighting cellular diversity.
• Detected extensive signaling interactions among stromal, epithelial, endothelial, and immune cell populations, emphasizing the complexity of the tumor microenvironment.
• Extracted 123 candidate genes from 31 fibroblast-associated modules identified by hdWGCNA, providing a foundation for further research.
• DRAM1 was selected for validation and showed elevated expression in CRC tissues and cell lines, indicating its potential significance.
• Loss-of-function assays indicated that silencing DRAM1 enhanced CRC cell proliferation, migration, invasion, and xenograft growth, suggesting its role in tumor suppression.

Interpretation:

Increased DRAM1 expression may reflect a compensatory stress-response program, indicating its potential role in tumor biology beyond a purely oncogenic function.

Limitations:

• The direct role of DRAM1 in fibroblast-mediated stromal-immune regulation requires further investigation to fully understand its implications in CRC.

Conclusion:

This study identifies DRAM1 as a candidate gene linked to fibroblast-related transcriptional networks in CRC, suggesting a tumor-restraining role in epithelial tumor cell models, which may have therapeutic implications.

Attribution Notice

This content is an AI-generated, fully rewritten summary based on a published scholarly article. It does not reproduce the original text and is not a substitute for the original publication. Readers are encouraged to consult the source for full context, data, and methodology.