Change of dual-specificity phosphatase 1 expression in tamoxifen-resistant human breast cancer

Objective: To investigate whether dual-specificity phosphatase 1 (DUSP1) plays a role in tamoxifen (TAM) resistance and survival of breast cancer patients. Methods: We analyzed DUSP1 mRNA expression in 1215 patient samples in TCGA database and the correlation between DUSP1 mRNA and patient survival using online database. We also investigated the DUSP1 protein level in paired samples from TAM-resistant patients by IHC staining. Results: DUSP1 mRNA was significantly decreased in breast cancer tissue compared with normal breast tissue (P<0.001); DUSP1 showed the highest expression in luminal A subtype in all five breast cancer subtypes (P<0.001). Increased DUSP1 mRNA was associated with better overall survival (P<0.05) and relapse-free survival (P<0.001) in breast cancer patients, and was correlated with better relapse-free survival in breast cancer patients receiving endocrine therapy (P<0.001). There was no significant difference in DUSP1 protein level between primary tumor tissue and TAM-resistant tumor tissue from 8 paired TAM resistant patients (P>0.05). Conclusion: Increased level of DUSP1 mRNA expression was associated with significantly increased probability of relapse-free survival in patients who received endocrine therapy. The expression of DUSP1 protein in primary tumor tissue and TAM-resistant tumor tissue from the 8 paired samples did not significantly differ, which indicates the role that DUSP1 plays in TAM resistance requires larger sample scale and further investigation in cellular and molecular biology.