Clinical implication of ZEB-1 and E-cadherin expression in hepatocellular carcinoma (HCC)

Abstract

BackgroundWhile 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.MethodsA 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.ResultsWith 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).ConclusionsPositive 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.

Long Noncoding RNA HOST2 Promotes Epithelial-Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway

“…The loss of E-cadherin enables metastasis by disrupting intercellular contacts, an early step in metastatic dissemination [29]. Moreover, one of the hallmarks of EMT is the downregulation of E-cadherin (a cell adhesion molecule), which is a transmembrane protein involved in the establishment of stable adherent junctions; other hallmarks of EMT include the upregulation of mesenchymal markers (vimentin, fibronectin and/or N-cadherin) [47]. Additionally, we also found that in the HOST2 mimic group, the protein levels of Snail, Slug and Twist were increased but that the protein level of Zeb1 was decreased.…”

Impact of positive ZEB1 expression in patients with epithelial ovarian carcinoma as an oncologic outcome-predicting indicator

“…Spoelstra et al (22) revealed that ZEB1 was aberrantly expressed in carcinoma cells of aggressive poorly-differentiated endometrioid carcinomas and other kinds of aggressive endometrial cancers, including uterine serous carcinomas. In addition, Hashiguchi et al (8) reported the clinical effect of ZEB1 and E-cadherin expression in 108 patients with primary hepatocellular carcinoma. They demonstrated that positive immunohistochemical activity of ZEB1 was significantly correlated with a reduced expression of E-cadherin, and those with positive ZEB1/reduced E-cadherin expression particularly showed a poorer overall survival.…”

“…Also, it has been reported to be a major transcriptional factor in cancer progression/ metastasis (5). In fact, earlier studies reported that ZEB1 promotes tumor invasiveness and metastasis and is correlated with a poorer clinical prognosis in patients with several solid cancers (6)(7)(8). According to the prior report from Siebzehnrubl et al (9), ZEB1 is an important marker of glioblastoma recurrence, including the capability of evading chemotherapy, suggesting that this molecule acts in both glioblastoma invasion and chemoresistance.…”

Expression of E-cadherin in oral lichen planus

“…There is also evidence that cleavage fragments of E-cadherin are involved in cellular junction destruction, cell migration, invasion and abnormal signal activation, which indicates a promoting role of E-cadherin in cancer progression. Studies have found the abnormal expression of E-cadherin in a variety of malignant tumors of epithelial origin, such as colorectal carcinoma, gastric carcinoma, esophageal carcinoma, hepatoma, lung neoplasms, breast carcinoma, prostate cancer and endometrial malignant tumors (12)(13)(14). This reveals that E-cadherin might have a close association with the pathological features and biological behavior of tumors.…”