A literature-guided integrative transcriptomic analysis framework for prioritizing angiogenesis-associated genes...

Area of Science:

• Oncology
• Genomics
• Bioinformatics

Background:

• Angiogenesis is crucial for cancer, but current gene prioritization methods miss non-canonical regulators.
• Existing approaches often rely on predefined gene sets or canonical pathways, limiting discovery.

Purpose of the Study:

• To develop a literature-guided integrative transcriptomic framework for identifying novel angiogenesis-associated genes across diverse cancer types.
• To prioritize candidate genes based on convergent evidence from multiple data sources, moving beyond predefined pathways.

Main Methods:

• Integrated bibliometric trend profiling, pan-cancer gene expression, survival analysis, tumor microenvironment characterization, and functional enrichment.
• Prioritized candidate genes based on convergence across complementary evidence layers, including cadherin 2 (CDH2).
• Validated findings in independent glioma cohorts, assessing CDH2's relationship with vascular endothelial growth factor A (VEGFA) and clinical outcomes.

Main Results:

• The framework consistently identified CDH2 as a non-canonical angiogenesis-associated signal across cancer types.
• CDH2 expression correlated with extracellular matrix organization, cell-cell adhesion, and structural remodeling, aligning with stromal and vascular features.
• In glioma cohorts, CDH2 showed context-dependent associations with VEGFA and was linked to worse overall survival in a subset of lower-grade gliomas.

Conclusions:

• The developed framework effectively prioritizes angiogenesis-associated genes beyond canonical regulators.
• Structure-oriented, non-canonical angiogenesis programs, exemplified by CDH2, represent reproducible biological signals in cancer.
• Highlights the importance of integrating diverse data types for comprehensive understanding of cancer biology.