Exploration of the Shared Gene Signatures and Molecular Mechanisms Between Breast Cancer and Endometriosis

Abstract

Background Globally, breast cancer (BC) is the most common type of cancer and the second leading cause of cancer-related deaths among women. Early diagnosis and survival outcomes will be improved through the identification of modifiable risk factors and the development of better disease management strategies. There are many similarities between endometriosis and breast cancer, both in terms of risk factors and developmental characteristics. Thus, it would be beneficial to explore the common mechanisms behind the onset of BC and endometriosis to develop more effective intervention strategies in the future. In this study, bioinformatics was used to explore the key molecules and pathways that mediate the co-occurrence of BC and endometriosis. Method From the Gene Expression Omnibus (GEO) database, datasets for BC (GSE15852) and endometriosis (GSE5108) were downloaded. By using the GEO2R online tool, we were able to identify the differentially expressed genes (DEGs) between two diseases. Afterward, a protein-protein interaction network (PPI) was constructed based on DEG enrichment analysis. Additionally, the hub genes were identified using the STRING database and Cytoscape software. We investigated the relationship between hub gene expression levels and clinical expression, pathological stage, age, and prognosis. As a final step, transcription factor interaction, stemness score, and immune cell infiltration analysis were conducted on hub genes in BC. Results We identified 33 overlapping DEGs (18 downregulated genes and 15 upregulated genes) for further analysis. The significant functional pathways of DEGs were enriched in regulating the pluripotency of stem cells and the mis-regulation of transcription in cancer. Additionally, five key hub genes were identified, including HOXA10, PAX8, MSX1, FGFR1, and INHBA. Pathological stages, age, stemness score, and immune infiltration were associated with the expression level of hub genes. Conclusion A novel insight into the molecular mechanism of endometriosis complicated with BC is provided by the finding that HOXA10, PAX8, MSX1, FGFR1, and INHBA were hub genes for the co-occurrence of BC and endometriosis.