Correlations Between14-3-3ε Expression And Clinicopathological Factors And Prognosis In Patients With Esophageal Squamous Cell Carcinoma

Esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer related deaths worldwide. The incidence of esophageal squamous cell carcinoma (ESCC) is more frequent in China. ESCC has a very poor prognosis, with an overall5-year survival rate of about20%after surgery, which is largely due to late diagnosis. Yet the molecular mechanism during human esophageal squamous carcinogenesis remains unclear.14-3-3ε, an important member of14-3-3protein family, is up-regulated in various cancers and promotes the proliferation of cancer cells. In present study, we investigated the expression of14-3-3ε in esophageal squamous cell carcinoma (ESCC), and revealed its relationship with clinical characteristics.The14-3-3e expression in tumors and adjacent normal epithelia from72ESCC patients was detected by immunohistochemical staining. The expression of14-3-3ε protein was significantly up-regulated in tumors with77.8%positive and27.8%strong positive staining, compared with paired adjacent normal epithelia with43.1%positive and only2.8%strong positive staining (p<0.001). In a total of56positive staining tumors,14-3-3ε was detected in cytoplasm of37(66.1%), in nucleus of4(7.1%), in both cytoplasm and nucleus of15(26.8%) cases. Whereas, in a total of31positive staining normal epithelia,14-3-3s was detected in cytoplasm of0, in nucleus of13(41.9%), in both cytoplasm and nucleus of18(58.1%) cases (p<0.001). Furthermore, correlations of14-3-3s expression or their subcellular localization and clinicopathological factors were analyzed using Chi-squared test. Statistical analysis revealed that strong14-3-3ε expression was correlated with lymph node metastasis (p=0.028) and lower5-year survival (p=0.018). In addition, survival curves were generated according to the Kaplan-Meier method, and the statistical analysis was performed by Log-Rank test. The survival curves calculated by Kaplan-Meier method further showed that the patients with strong14-3-3ε expression had a shorter survival than patients with negative or weak14-3-3ε expression (Log Rank, p=0.031). No correlation was found between subcellular localization of14-3-3ε in tumor cells and clinicopathologic factors and prognosis of ESCC patients.In conclusion,the14-3-3ε expression is significantly up-regulated in ESCCs. It was usually located in cytoplasm of tumor cells, but nucleus of normal epithelia. Strong expression of14-3-3ε in tumors is associated with lymph node metastasis and considered as an unfavorable prognostic factor for ESCC.