RESUMO
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.
RESUMO
As a member of the Eph family of receptor tyrosine kinases, EphA7 plays an important role in cancer. However, the expression and significance of Eph receptors in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we detected the expression of EphA7 by immunohistochemistry in a sample of 352 patients with ESCC, and aimed to investigate the expression status of EphA7 in ESCC and its impact on prognosis. The results showed that low EphA7 expression significantly correlated with lymph node metastases (N0: 29%; N1: 64%. p<0.001), poor degree of tumor differentiation (G1: 31%; G2: 49%; G3: 58%. p=0.009) and pTNM staging (I+II: 33%; III+IV: 58%. p<0.001). Furthermore, in a combined analysis, patients with low EphA7-expressing tumors showed a shorter overall survival than those with high expression, resulting in a five-year overall survival rate of 47.4% vs. 52.6%, respectively (p=0.016). Consequently, patients with a low EphA7 expression have poorer prognosis in ESCC compared with those manifesting high expression.
RESUMO
As a member of the catenin family, expression of δ-catenin and its clinical implication in numerous tumors remain unclear. In the present study, expression of δ-catenin in esophageal squamous cell carcinoma (ESCC) and its correlations with patient prognosis were explored. We detected the expression of δ-catenin, by immunohistochemistry, in ESCC tissues from 299 cases and analyzed the correlation between δ-catenin expression and patient clinicopathological features. Compared with a lack of expression in adjacent normal esophageal epithelium (0%, 0/47), the frequency of δ-catenin protein was increased in ESCC tissues to 41.5% (124/299, P < .001) and expression correlated with TNM stage and lymph node metastasis (P = .025 and .019, respectively). Furthermore, Kaplan-Meier survival analysis revealed that patients with high δ-catenin expression had shorter survival than patients with low expression (P = .010), and multivariate Cox analysis revealed that high δ-catenin expression was also an independent prognostic factor (P = .001). In transwell assays, migration of ESCC cells was enhanced by δ-catenin overexpression, whereas proliferation of ESCC cells was unchanged. Together, our results suggest that δ-catenin acts as an oncoprotein when overexpressed in ESCC, and its expression is associated with poor prognosis and malignant cell behavior.
