ZEB-1 和 E-钙黏蛋白在肝细胞癌（HCC）中的表达的临床意义。
Clinical implication of ZEB-1 and E-cadherin expression in hepatocellular carcinoma (HCC).
机构信息
Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan.
出版信息
BMC Cancer. 2013 Dec 5;13:572. doi: 10.1186/1471-2407-13-572.
BACKGROUND
While recent research has shown that expression of ZEB-1 in a variety of tumors has a crucial impact on patient survival, there is little information regarding ZEB-1 expression in hepatocellular carcinoma (HCC). This study investigated the co-expression of ZEB-1 and E-cadherin in HCC by immunohistochemistry and evaluated its association with clinical factors, including patient prognosis.
METHODS
A total of 108 patients with primary HCC treated by curative hepatectomy were enrolled. ZEB-1 expression was immunohistochemically categorized as positive if at least 1% cancer cells exhibited nuclear staining. E-cadherin expression was divided into preserved and reduced expression groups and correlations between ZEB-1 and E-cadherin expression and clinical factors were then evaluated.
RESULTS
With respect to ZEB-1 expression, 23 patients were classified into the positive group and 85 into the negative group. Reduced E-cadherin expression was seen in 44 patients and preserved expression in the remaining 64 patients. ZEB-1 positivity was significantly associated with reduced expression of E-cadherin (p = 0.027). Moreover, significant associations were found between ZEB-1 expression and venous invasion and TNM stage. ZEB-1 positivity was associated with poorer prognosis (p = 0.025). Reduced E-cadherin expression was significantly associated with intrahepatic metastasis and poorer prognosis (p = 0.047). In particular, patients with both ZEB-1 positivity and reduced E-cadherin expression had a poorer prognosis (p = 0.005). Regardless of E-cadherin status, ZEB-1 was not a significant prognostic factor by multivariate analysis. There was no statistical difference in overall survival when E-cadherin expression was reduced in the ZEB-1 positive group (p = 0.24).
CONCLUSIONS
Positive ZEB-1 expression and loss of E-cadherin expression are correlated with poor prognosis in HCC patients and malignancy of ZEB-1 positive tumors involves EMT.
背景
虽然最近的研究表明，ZEB-1 在各种肿瘤中的表达对患者的生存有至关重要的影响，但关于肝细胞癌（HCC）中 ZEB-1 的表达的信息却很少。本研究通过免疫组织化学方法研究了 HCC 中 ZEB-1 与 E-钙黏蛋白的共表达，并评估了其与临床因素的相关性，包括患者预后。
方法
共纳入 108 例接受根治性肝切除术治疗的原发性 HCC 患者。如果至少有 1%的癌细胞显示核染色，则 ZEB-1 的表达通过免疫组化被归类为阳性。E-钙黏蛋白表达分为保留和减少表达组，然后评估 ZEB-1 与 E-钙黏蛋白表达与临床因素之间的相关性。
结果
就 ZEB-1 表达而言，23 例患者被归类为阳性组，85 例患者被归类为阴性组。44 例患者 E-钙黏蛋白表达减少，64 例患者 E-钙黏蛋白表达保留。ZEB-1 阳性与 E-钙黏蛋白表达减少显著相关（p=0.027）。此外，ZEB-1 表达与静脉侵犯和 TNM 分期之间存在显著相关性。ZEB-1 阳性与预后不良相关（p=0.025）。E-钙黏蛋白表达减少与肝内转移和预后不良显著相关（p=0.047）。特别是，同时具有 ZEB-1 阳性和 E-钙黏蛋白表达减少的患者预后更差（p=0.005）。无论 E-钙黏蛋白状态如何，ZEB-1 在多变量分析中均不是显著的预后因素。在 ZEB-1 阳性组 E-钙黏蛋白表达减少的情况下，总生存率无统计学差异（p=0.24）。
结论
ZEB-1 阳性表达和 E-钙黏蛋白表达缺失与 HCC 患者的不良预后相关，并且 ZEB-1 阳性肿瘤的恶性程度涉及 EMT。
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