An Association Study Between VDR and HER2 in Breast Cancers Reveals the Potential of Combined Diagnosis and Prognosis

Background: Breast cancer is generally acknowledged as a heterogeneous disease, with complete characterization and underlying technologies available to predict outcomes. Biomarkers, especially the human epidermal growth factor receptor 2 (HER2), are keys to characterize breast cancer and optimize the patients’ clinical outcomes. Vitamin D has an anti-cancer effect in breast cancer, which is related to the expression level of the vitamin D receptor (VDR). Despite these remarkable achievements, there is limited focus on the combined effects of VDR and HER2, which may provide specific diagnostic and prognostic potential in breast cancers. Results: In this study, we evaluated the association between VDR and HER2-status-related clinical prognostic characters by processing the breast cancer data of 2433 cases obtained from cBioPortal , discovering a high and positive correlation between VDR and HER2 in breast cancer. We also found substantial genes that are significantly correlated with both VDR and HER2 expressions. Those negatively correlated are enriched with pathways involving translations, showing a quite different mechanism from previous studies. Moreover, the survival analysis reveals that higher VDR copy number aberration (CNA) or HER2 expression shows significantly higher death rates in breast cancer patients. Conclusion: Our study reveals new mechanisms of coordinated function between VDR and HER2 in repressing cell translation, and prognosis or therapies targeted to VDR CNA and HER2 expression involving cell translations may be a potentially combined strategy in treating breast cancer.