Association between 5-lipoxygenase expression, and malignant behaviors and poor prognosis in esophageal squamous cell carcinoma

作者:Bai, Chun-Ying; Zhang, Jun-Yi; Shi, Tie-Wei; Bai, Yu-Qin; Wu, Bing-Li; Du, Ze-Peng; Wu, Zhi-Yong; Xu, Xiu-E; Wang, Shao-Hong; Wu, Jian-Yi; Te, Rui-Yun; Zhang, Jing-Yi; Xu, Li-Yan*; Li, En-Min*
来源:Oncology Letters, 2018, 15(6): 9353-9360.
DOI:10.3892/ol.2018.8527

摘要

5-lipoxygenase (5-LO) catalyzes the first step of arachidonic acid metabolism to inflammatory mediator leukotrienes. The present study assessed 5-LO expression in esophageal squamous cell carcinoma (ESCC) tissue specimens for associations with clinicopathological and survival data from patients, then explored 5-LO activity in ESCC cells in vitro. 5-LO expression was detected in tissue microarrays containing 297 ESCC samples using immunohistochemistry. Kaplan-Meier curves were used to analyze the survival significance of 5-LO expression and relative risk was evaluated using the multivariate Cox proportional hazards model. Cultured tumor cells were subjected to gene transfection, western blotting, and cell migration and proliferation assays. 5-LO protein was primarily expressed in normal cell cytoplasm and/or membrane, and never in the whole cytoplasm, whereas 5-LO was expressed diffusely in ESCC tissues with nearly homogeneous whole-cytoplasm staining. 5-LO expression was significantly associated with tumor regional lymph node metastasis (P=0.013) and pTNM stage (P=0.004). 5-LO expression was associated with poor overall survival (P=0.029). Multivariate analysis demonstrated that 5-LO overexpression was an independent prognostic factor for ESCC patients (P=0.041). Furthermore, the inhibition of 5-LO expression reduced ESCC cell viability and migration in vitro. These data provide further evidence that the upregulation of 5-LO expression is associated with advanced stages of disease and poor ESCC prognosis, and that 5-LO expression may independently predict overall survival in patients with ESCC. The inhibition of 5-LO expression reduced ESCC malignant behavior in vitro.