DDR2-COL11A1 Transcriptional Coupling as a Candidate Therapeutic Target in Colorectal Cancer: Integrative Transcriptomic and Deep Learning Validation
Yasemin Başbınar, Ömer Akgüller, Asım Leblebici, Gizem Çalıbaşı Koçal, Mehmet Ali Balcı, Zerrin Isik, Hülya Ellidokuz
TL;DR
This study identifies DDR2-COL11A1 transcriptional coupling as a key mechanism in colorectal cancer progression and a potential new therapeutic target.
Contribution
The paper introduces DDR2-specific transcriptional coupling as a novel mechanism in colorectal cancer, validated through deep learning and transcriptomic analysis.
Findings
DDR2-COL11A1 coupling intensifies significantly from normal to cancerous tissue, with a 2.59-fold increase in correlation.
Deep learning models achieved 93.14% accuracy in classifying disease stages, with DDR2-COL11A1 identified as the most important gene interaction.
COL11A1 is upregulated 1.99-fold in cancer, despite stable DDR2 expression, suggesting coupling efficiency as the key mechanism.
Abstract
Extracellular matrix (ECM) remodeling is a hallmark of colorectal cancer progression, yet the transcriptional mechanisms coordinating collagen deposition and matrix metalloproteinase activation remain incompletely understood. We performed integrated computational analysis of 680 samples across normal mucosa, adenoma, and carcinoma stages to characterize discoidin domain receptor (DDR)-mediated transcriptional networks during tumorigenesis. Stage-stratified correlation analysis of fourteen pathway genes revealed profound divergence between DDR1 and DDR2; DDR1 correlations remained weak across all stages, while DDR2 correlations strengthened 2.59-fold from normal to carcinoma. DDR2-COL11A1 exhibited the most dramatic coupling intensification, increasing from R2=0.007 in normal tissue to R2=0.549 in carcinoma, accompanied by 1.99-fold COL11A1 upregulation. Remarkably, pathway activation…
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Taxonomy
TopicsCell Adhesion Molecules Research · Proteoglycans and glycosaminoglycans research · Wnt/β-catenin signaling in development and cancer