Deciphering the molecular mechanism and crosstalk between Parkinson's disease and breast cancer through multi-omics and drug repurposing approach

Abstract

Epidemiological studies indicate a higher occurrence of breast cancer (BRCA) in patients with Parkinson's disease. However, the exact molecular mechanism is still not precise. Herein, we tested the hypothesis that this inverse comorbidity result from shared genetic and molecular processes. We conducted an integrated omics analysis to identify the common gene signatures associated with PD and BRCA. Secondly, several dysregulated biological processes in both indications were analyzed by functional enrichment methods, and significant overlapping processes were identified. To establish common regulatory mechanisms, information about transcription factors and miRNAs associated with both the disorders was extracted. Finally, disease-specific gene expression signatures were compared through LINCS L1000 analysis to identify potential repurposing drugs for PD. The potential repurposed drug candidates were then correlated with PD-specific gene signatures by Cmap analysis. In conclusion, this study highlights the shared genes, biological pathways and regulatory signatures associated with PD and BRCA with an improved understanding of crosstalk involved. Additionally, the role of therapeutics was investigated in context with their comorbid associations. These findings could help to explain the complex molecular patterns of associations between PD and BRCA.