Prognostic significance of preoperative IKBKE expression in esophageal squamous cell carcinoma.
Prognostic significance of preoperative IKBKE expression in esophageal squamous cell carcinoma.
复制标题
食管鳞癌术前 IKBKE 表达的预后意义
DOI：
10.2147/ott.s156818
复制
发表时间：
2018
影响因子：
4
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Yang W;Qu Y;Tan B;Jia Y;Wang N;Hu P;Wang J
IκB激酶A（IKBKE; IKKε）是核因子-κB激酶抑制剂家族的成员，在几种人类癌症中上调，包括乳腺癌、前列腺癌和卵巢癌。食管鳞状细胞癌是最常见、最具侵袭性的恶性肿瘤之一，预后极差。然而，IKBKE在ESCC中的表达状态仍不清楚，其潜在价值仍有待探索。应用免疫组化方法检测118例食管鳞癌手术切除标本中IKBKE蛋白的表达。术后3年以上定期电话随访。采用卡方检验、Kaplan-Meier法和考克斯比例风险回归模型分析IKBKE表达与食管鳞癌临床病理特征及预后的关系。石蜡包埋食管鳞癌组织中IKBKE表达率为61.9%（73/118）。其表达与肿瘤分化程度（p=0.045）和晚期TNM（病理肿瘤淋巴结转移）分期（p=0.023）显著相关。在单变量分析中，IKBKE表达与3年无病生存率（HR 1.804，95% CI 1.076-3.027; p=0.023）和总生存率（HR 2.118，95% CI 1.189-3.773; p=0.009）降低密切相关。同时，在多变量分析中，它被确定为3年无病生存期（HR 1.777，95%CI 1.034-3.054; p=0.037）和总生存期（HR 2.078，95%CI 1.138-3.796; p=0.017）的独立预后因素。我们的数据首次表明IKKε表达在ESCC中是一个高度复发的事件，并可能在预后评估中发挥关键作用。IKBKE上调与无病生存期和总生存期呈负相关。因此，IKBKE可以作为一个预后变量和潜在的治疗靶点，这种恶性肿瘤。
IκB kinase epsilon (IKBKE; IKKε), 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 IKBKE expression 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 IKBKE expression, 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, IKBKE expression 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 IKKε expression is a highly recurrent event in ESCC and could play a pivotal role in the evaluation of prognosis. IKBKE upregulation is negatively associated with disease-free survival and overall survival. Therefore, IKBKE could serve as a prognostic variable and potential therapeutic target for this malignancy.