12-lipoxygenase promotes tumor progress by TGF-β1-mediated epithelial to mesenchymal transition and predicts poor prognosis in esophageal squamous cell carcinoma

PURPOSE: To clarify the effect of 12-lipoxygenase/12-hydroxyeicosatetraeonic acid (12-LOX/12-HETE) on progress of esophageal squamous cell carcinoma (ESCC) and the possible mechanism. PATIENTS AND METHODS: We performed cell experiments including chemical treatment, transfection, Western blotting and transwell assay to investigate the function of 12-LOX/12-HETE. Slices of tumor tissues were obtained from ESCC patients treated in Qilu Hospital of Shandong University. Immunohistochemical (IHC) staining was done to find their correlation with prognosis and clinicopathological characteristics. RESULTS: In ESCC cells, inhibition of 12-LOX caused a decrease in transforming growth factor-β1 (TGF-β1)-mediated epithelial-mesenchymal transition (EMT) level, and abilities of migration and invasion were also inhibited. Nevertheless, the inhibition could be partly relieved when treated with 12-HETE or TGF-β1. Analyses of IHC staining indicated a positive correlation between the expression of 12-LOX and EMT level, and an inverse correlation between 12-LOX and overall survival (OS). Univariate and multivariate analyses further suggested that 12-LOX was an independent prognostic factor for ESCC patients. CONCLUSION: In conclusion, our study proved that 12-LOX/12-HETE-promoted tumor migration and invasion might partly be through TGF-β1-mediated EMT in ESCC, and 12-LOX could be a promising biomarker for predicting prognosis in ESCC patients.