Ezrin as a possible diagnostic and/or prognostic biomarker in mice lymphatic metastatic hepatocellular carcinoma in vivo

Abstract

Hepatocellular carcinoma (HCC) ranks in the top of cancers leading to death. Early diagnosis is the big challenge in the case of HCC. Our in vitro study showed that Ezrin expression in lymphatic metastasis hepatocellular carcinoma (LNM-HCC) was associated with the metastatic rate. Here we aim to evaluate Ezrin expression as diagnostic and/or prognostic biomarker of LNM-HCC in mice. Chinese inbred 615 mice, Hca-F and Hca-P cell lines were used in the study. Histological changes were determined by Hematoxylin and Eosin, while Ezrin expression was assessed by qRT-PCR, western blot, immunohistochemistry, and enzyme-linked immunosorbent assay. Ezrin expression in this study gives credit to our in vitro study which Ezrin expression was positively correlated with LNM-HCC and negatively with Annexin7 (A7) expression. The highest histological changes were observed in high metastatic primary/secondary tumors combined with high Ezrin expression. Ezrin and A7 are higher in total primary tumors than in total secondary tumors (P = 0.0001, P = 0.021), respectively. Ezrin expression was enhanced in Hca-P A7 down-regulated primary/secondary tumors (P = 0.004), whereas, Ezrin expression was suppressed in Hca-F A7 upregulated primary/secondary tumors. Serum ELISA indicated differential expression of Ezrin among the study groups (P ≤ 0.0001). Ezrin expression was higher in NC-Hca-F than NC-Hca-P (P ≤ 0.0001), suppressed in Hca-F A7 upregulation (P ≤ 0.0001) and in enhanced in Hca-P A7 down-regulation (P = 0.0001). In conclusion, Ezrin level may serve as a differential diagnostic and/or prognostic biomarker for high and low LNM-HCC and may be beneficial in the diagnosis of HCC disease. © 2017 BioFactors, 43(5):662-672, 2017.

Ezrin and E-cadherin expression profile in cervical cytology: a prognostic marker for tumor progression in cervical cancer

“…Proteins of the Ezrin/Radixin/Moesin (ERM) family, participate in the regulation of cell networks associated with tumor progression, through their interaction with membrane proteins, the actin cytoskeleton and signaling molecules, such as CD43, CD44, ICAM-1, ICAM-2 or EGFR [ 9 , 10 ]. Ezrin is the most studied member of the family, it is expressed in epithelial cells and its overexpression has been reported in breast cancer [ 11 ], prostate cancer [ 12 ], hepatocellular carcinoma [ 13 ], ovarian cancer [ 14 ], and endometrial cancer [ 15 ]. Ezrin overexpression is associated with poor prognosis and tumor invasiveness.…”

Moesin, an Ezrin/Radixin/Moesin Family Member, Regulates Hepatic Fibrosis

“…However, another ERM protein, ezrin, has been shown to be up-regulated in hepatocellular carcinomas (HCCs). (30,31) Although a function for ezrin in HCC was not elucidated, the data raise the possibility that mechanotransducing signals could play a role in HCC carcinogenesis.…”

“…There are at present no published data available on moesin expression in cholangiopathies, liver cancer, or fibrosing liver diseases, including primary biliary cholangitis, primary sclerosing cholangitis, and alcoholic and nonalcoholic steatohepatitis. However, another ERM protein, ezrin, has been shown to be up‐regulated in hepatocellular carcinomas (HCCs) . Although a function for ezrin in HCC was not elucidated, the data raise the possibility that mechanotransducing signals could play a role in HCC carcinogenesis.…”

Perspectives for Targeting Ezrin in Cancer Development and Progression

“…EZR expression was higher in tumor samples than hepatic tissues and associated with metastasis and differentiation degree [41,42]. High EZR levels have been significantly associated with advanced TNM stage, poor Edmondson's histological grade, macroscopic portal vein invasion, tumor recurrence, and extrahepatic recurrence, and are indepen-dently associated with poor overall survival [43,44].…”