Luminal A Breast Cancer Co-expression Network: Structural and Functional Alterations.

Area of Science:

• Genomics and Bioinformatics
• Cancer Molecular Biology
• Systems Biology

Background:

• Luminal A is the most common breast cancer subtype globally.
• Gene co-expression networks (GCNs) reveal molecular alterations in cancer.
• A previously observed phenomenon is the loss of inter-chromosomal (trans) co-expression in cancer GCNs, particularly in Luminal A.

Purpose of the Study:

• To investigate the functional implications of chromosomal homophily in Luminal A breast cancer GCNs.
• To explore potential mechanisms driving the loss of trans co-expression in cancer.
• To determine if network topology influences gene function in Luminal A.

Main Methods:

• Construction of GCNs for healthy and Luminal A breast cancer phenotypes.
• Module identification based on connectivity and chromosomal homophily (cis-/trans- interactions).
• Functional overrepresentation analysis, transcription factor binding site analysis, differential gene expression analysis, and copy number alteration (CNA) analysis.

Main Results:

• Trans communities in Luminal A GCNs exhibited more significantly enriched functional categories (e.g., angiogenesis, cell proliferation, adhesion) than cis communities.
• Specific transcription factors (FOXM1, CENPA, CIITA) were identified as key regulators of their respective communities.
• Copy number alterations, specifically deletions, were highly enriched in cis communities, suggesting a role in the loss of trans co-expression.

Conclusions:

• Network topology significantly influences gene function in Luminal A breast cancer.
• Multiple mechanisms, including CNAs and differential gene expression, appear to contribute to the loss of trans co-expression.
• The loss of long-distance co-expression warrants further investigation as a potential novel hallmark of cancer.