Subtype-specific network organization of molecular complexes in breast cancer

Breast cancer, a leading cause of death in women, is a complex heterogeneous disease comprising multiple molecular subtypes with different treatment responses and hence clinical outcomes. The present study aims to gain a deeper insight into the disease complexities at the level of molecular subtypes. For this, first, three subtype networks of breast cancer, viz., ER-/HER2-, ER+/HER2-, and HER2+, were constructed utilizing mRNA expression profiles of tumor tissues. Subsequently, these networks were used to construct three exclusively subtype-specific networks. Further, the mRNA expression profiles of all three subtypes were analyzed using differential correlations based on z-statistics of the F-test. Finally, functional enrichment analysis was carried out to elucidate functions and processes of important genes involved in subtype networks. From this analysis, it was observed that these subtype networks share a commonality among them in terms of preserved patterns. However, these networks possess specific patterns that result in exclusively subtypespecific networks having unique sets of wiring among the genes. Additionally, the significantly differentially correlated gene pairs between two subtypes demonstrate subtype-specific expressional patterns which make them different at the molecular level. Furthermore, the network analysis also revealed ER-/HER2--specific genes, viz., LUM, RARB, and ERCC6. Thus, the present analysis provides new insights for further research on breast cancer subtypes and hence the development of the most effective diagnosis and treatment.