Prognostic significance of preoperative IKBKE expression in esophageal squamous cell carcinoma

IκB kinaseepsilon ( IKBKE; IKKe), a member of the nuclear factor-κB kinase inhibitor family, is upregulated in several human cancers, including breast cancer, prostate cancer, and ovarian cancer. Esophageal squamous cell carcinoma (ESCC) is one of the most common and most aggressively malignant cancers with dismal prognosis. However, the state of IKBKEexpression in ESCC is still unknown and its potential value remains unexplored.IKBKE protein expression was evaluated by immunohistochemistry in 118 paraffin specimens of ESCC treated by curative surgery. All patients were regularly followed up by telephone over 3 years after surgery. The chi-square test, Kaplan-Meier method, and Cox proportional hazard regression model were used to analyze the relationship of IKBKEexpression, clinicopathological characteristics, and prognostic value for ESCC.IKBKE expression was 61.9% (73/118) in paraffin-embedded archived ESCC. Its expression was significantly associated with tumor differentiation grade (p=0.045) and advanced TNM (pathologic tumor node metastasis) stages (p=0.023). In univariate analysis, IKBKEexpression was closely associated with decreased 3-year disease-free survival (HR 1.804, 95% CI 1.076-3.027; p=0.023) and overall survival (HR 2.118, 95% CI 1.189-3.773; p=0.009). Meanwhile, in multivariate analysis it was identified as an independent prognostic factor for 3-year disease-free survival (HR 1.777, 95% CI 1.034-3.054; p=0.037) and overall survival (HR 2.078, 95% CI 1.138-3.796; p=0.017).Our data indicated for the first time that IKKe expression is a highly recurrent event in ESCC and could play a pivotal role in the evaluation of prognosis. IKBKEupregulation is negatively associated with disease-free survival and overall survival. Therefore, IKBKEcould serve as a prognostic variableand potential therapeutic target for this malignancy.