Topological, functional, and structural analyses of protein-protein Interaction networks of breast cancer lung and brain metastases

Abstract

Breast cancer is the second most common cause of death among women. However, it is not deadly if the cancerous cells remain in the breast. The life threat starts when cancerous cells travel to other parts of body like lung, liver, bone and brain. So, most breast cancer deaths derive from metastasis to other organs. In this study, we introduce novel proteins and cellular pathways that play important roles in brain and lung metastases of breast cancer using Protein-Protein Interaction (PPI) networks. Our topological analysis identified genes such as RPL5, MMP2 and DPP4 which are already known to be associated with lung or brain metastasis. Additionally, we found four and nine novel candidate genes that are specific to lung and brain metastases, respectively. The functional enrichment analysis showed that KEGG pathways associated with the immune system and infectious diseases, particularly the chemokine signaling pathway, are important for lung metastasis. On the other hand, pathways related to genetic information processing were more involved in brain metastasis. By enriching the traditional PPI network with protein structural data, we show the effects of mutations on specific protein-protein interactions. By using the different conformations of protein CXCL12, we show the effect of H25R mutation on CXCL12 dimerization.