DDR2-COL11A1 Transcriptional Coupling as a Candidate Therapeutic Target in Colorectal Cancer: Integrative...

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Extracellular matrix (ECM) remodeling is crucial in colorectal cancer (CRC) progression.
• Transcriptional regulation of ECM components and matrix metalloproteinases in CRC is not fully understood.

Purpose of the Study:

• To investigate discoidin domain receptor (DDR)-mediated transcriptional networks in colorectal tumorigenesis.
• To elucidate the role of DDR1 and DDR2 in coordinating ECM remodeling during CRC progression.

Main Methods:

• Integrated computational analysis of 680 samples across normal, adenoma, and carcinoma stages.
• Stage-stratified correlation analysis of pathway genes and deep neural network classification.
• SHAP analysis to identify key gene interactions for cancer classification.

Main Results:

• DDR2 showed significantly strengthened correlations with pathway genes from normal to carcinoma, unlike DDR1.
• DDR2-COL11A1 coupling intensified dramatically in carcinoma, with increased COL11A1 expression.
• Pathway activation occurred despite stable DDR2 expression, highlighting enhanced transcriptional coupling efficiency.
• Deep neural networks achieved 93.14% accuracy in distinguishing CRC stages, with DDR2-COL11A1 identified as a key interaction.

Conclusions:

• DDR2-specific transcriptional coupling is a critical mechanism in colorectal cancer progression.
• COL11A1 is a key downstream target regulated by DDR2-mediated coupling.
• Therapeutic strategies targeting coupling efficiency, not just receptor abundance, may be beneficial for CRC treatment.