Bioinformatics screening identifies USP9X as a pathogenic gene underlying thyroid and breast cancer comorbidity

The co-occurrence of thyroid cancer (TC) and breast cancer (BC) has attracted much attention in recent years. The aim of the study was to explore the potential molecular mechanisms in the comorbidity of TC and BC. We identified the differentially expressed genes (DEGs) for TC and BC using the TCGA database and screened the common driver genes for the comorbidity of TC and BC. Immunohistochemical staining was performed to verify the expression of the common gene (USP9X) in double primary cancers (co-occurrence of TC and BC). Migration, invasion and colony formation assays were used to evaluate the role of USP9X in TC and BC cells in vitro. In the present study, we confirmed 8 driver genes shared by TC and BC through bioinformatics analysis. In samples with co-occurring TC and BC, USP9X immunoreactivity was detected in 100% (14/14) TC and 100% (14/14) BC samples. Interfering with USP9X expression could inhibit the colony formation, migration and invasion abilities of TC and BC cells. Protein-protein interaction network analysis revealed USP9X/MCL-1 and USP9X/NUAK1 might be molecular pathways involved in the comorbidity of TC and BC. Our findings suggest that USP9X overexpression is a molecular event involved in the comorbidity of TC and BC and it could be a promising therapeutic target.