Dual-specificity
protein phosphatase 4 (DUSP4), a negative regulator of extracellular-regulated
kinase activity, is a potential mediator of resistance to
chemotherapy and a
tumor suppressor. The aim of this study is to clarify the association between DUSP4 gene expression and clinical outcome in patients with
colorectal cancer. Patients who underwent surgery for
colorectal cancer were enrolled in this study (n = 212). We investigated DUSP4 gene expression by real-time reverse transcription polymerase chain reaction in
colorectal cancer tissue and paired normal mucosa. Immunohistochemical analyses of DUSP4 and ERK1/2 were also conducted. Additionally, we examined the relationship between gene expression and KRAS mutation in 74 of the 212 patients. DUSP4 expression in
tumor tissues was significantly higher than that in matched normal mucosa (P < 0.0001). Decreased DUSP4 expression was significantly associated with advanced T classification, lymphatic invasion, vascular invasion, advanced stage, and liver and lung
metastases. Logistic regression analysis revealed that decreased DUSP4 expression was an independent risk factor for synchronous distant
metastases (P = 0.006). Increased DUSP4 expression was significantly associated with better prognosis (P = 0.0162). Immunohistochemical examination showed DUSP4 expression in the nucleus and cytoplasm of
cancer cells, and no correlation was observed between DUSP4 and ERK1/2 expression. There was no significant correlation between DUSP4 expression and KRAS mutation. In conclusion, DUSP4 expression in
colorectal cancer was negatively correlated with factors reflecting
tumor progression, including distant
metastases. Our data suggest that DUSP4 may act as a
tumor suppressor in
colorectal cancer.