Dual specificity phosphatase 5 is a novel prognostic indicator for patients with advanced colorectal cancer

Am J Cancer Res. 2016 Oct 1;6(10):2323-2333. eCollection 2016.

Abstract

Dual specificity phosphatase 5 (DUSP5) is a negative regulator of Mitogen-activated protein kinase (MAPK) signaling pathway and has recently been identified as a tumor suppressor in several human malignancies. However, its clinical significance in colorectal cancer (CRC) remains unclear. In this study, we aimed to investigate the potential utility of DUSP5 as a novel biomarker for progression indication and chemotherapy benefit in CRC patients. Through quantitative real time-polymerase chain reaction and western blot, we determined that DUSP5 expression is dramatically lower in CRC tissues than that in matched normal tissues. The statistical analysis based on immunohistochemistry revealed that DUSP5 expression is significantly correlated with tumor differentiation, TNM stage, lymph node metastasis and distant metastasis. For the whole study cohort, patients with high DUSP5 expression had a better CRC-specific and disease-free survival than those with low DUSP5 expression and DUSP5 expression is an independent prognostic factor for patient survival. In subgroup analysis, DUSP5 has no prognostic significance in low-risk stage II patients, but could predict treatment response in high-risk stage II and stage III/IV patients who received standard FOLFOX chemotherapy scheme. Finally, the correlation analysis suggested that DUSP5 expression is associated with Epithelial-to-Mesenchymal Transition (EMT) phenotype in CRC tissues, suggesting that downregulated DUSP5 may contribute to poor prognosis partly by involving EMT. Taken together, our study proposes that DUSP5 is a promising biomarker for predicting CRC progression and advanced patients with high DUSP5 expression appear to benefit from standard FOLFOX chemotherapy scheme.

Keywords: DUSP5; EMT; colorectal cancer; prognosis.