Deciphering crucial genes in triple negative breast cancer and non-alcoholic fatty liver disease pathogenesis and drug repurposing: A systems biology approach

Background: It has been widely recognized that triple negative breast cancer (TNBC) and non-alcoholic fatty liver disease (NAFLD) are related, but underlying mechanisms remain unclear. This study investigated the possible co-pathogenesis and prognostic connections between TNBC and NAFLD and relevant hub genes associated with them. Aim: Using a systems biology approach, we identify crucial genes that contribute to TNBC and NAFLD to investigate new biomarkers and propose new medicines. Methods: Cytoscape was used to construct protein-protein interaction (PPI) networks and functional enrichment analysis to determine which molecules were crucial. Disease genes from the DisGeNET and STRING databases were used to construct disease networks. A network of gene-drug interactions and gene-disease associations was also created for the purpose of suggesting drugs and mapping diseases. Results: Using the STRING database, 343 common genes between TNBC and NAFLD were used to construct a PPI network. This network has 182 nodes and 2591 edges and 3 clusters along with 26 hub-bottleneck genes. Enrichment of these gens lead to recognition of locomotion, membrane-enclosed lumen, molecular function regulator, and pathways in cancer as top biological process, cellular component, molecular function, and pathway, respectively. Drug-gene analysis revealed that Cisplatin, carboplatin, sorafenib, cetuximab, paclitaxel, gemcitabine, and etoposide have the highest degree of interaction with key genes. Conclusion: In silico data analysis approaches indicated that TNBC and NAFLD share common genes and signaling pathways. Additionally, we identified key drugs that target both TNBC and NAFLD genes.