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上皮-间充质转化标志物在 HCV 相关肝细胞癌中的作用:一项多变量随访研究。

Epithelial-Mesenchymal Transition Markers in HCVAssociated Hepatocellular Carcinoma: A Multivariate Follow Up Study.

机构信息

Department of Pathology, Faculty of Medicine, Ain Shams University, Cairo Egypt.

October University for Modern Science and Arts, Giza, Egypt.

出版信息

Asian Pac J Cancer Prev. 2022 Mar 1;23(3):839-849. doi: 10.31557/APJCP.2022.23.3.839.

Abstract

OBJECTIVE

Validated markers to predict recurrence after surgical resection of hepatocellular carcinoma (HCC) are needed. Little data is available regarding epithelial-mesenchymal transition (EMT) markers in HCC. The objective of this study was to investigate the expression of EMT markers and their correlation with clinicopathological variables and survival in hepatitis C virus (HCV)-associated HCC.

METHODS

This longitudinal study included 109 cases of HCV-associated HCC treated with surgical resection. Nine different EMT markers (vimentin, E-cadherin, N-cadherin, Stat3, Snail1, Slug, Twist1, Zeb1 and integrin α5) were evaluated on liver tissue from HCC cases. Twenty fresh HCC samples from the studied cases were used for gene expression of EMT markers by quantitative real time polymerase chain reaction (PCR).

RESULTS

EMT markers expression was 71%, 25%, 26%, 27%, 9%, 4%, 72%, 47%, 87% for vimentin, E-cadherin, N-cadherin, Stat3 snail1, slug, twist1, Zeb1 and integrin α5 respectively.  EMT mRNA in HCC tissues correlated with protein expression by 50-70%.  Vimentin was independent predictor of large tumor size (P=0.001), high risk of recurrence (HRR) (P=0.006) and shorter disease free survival (P=0.03) in multivariate analysis.  Reduced E-cadherin was a predictor of HRR (P=0.002).

CONCLUSION

Vimentin and E-cadherin were the most powerful prognostic EMT markers in HCV-associated HCC in prediction of recurrence.

摘要

目的

需要有效的标志物来预测肝细胞癌 (HCC) 手术后的复发。关于 HCC 中的上皮-间充质转化 (EMT) 标志物,数据很少。本研究的目的是探讨 EMT 标志物的表达及其与丙型肝炎病毒 (HCV) 相关 HCC 的临床病理变量和生存的相关性。

方法

本纵向研究纳入了 109 例接受手术切除治疗的 HCV 相关 HCC 病例。评估了 HCC 病例肝组织中的 9 种不同的 EMT 标志物(波形蛋白、E-钙黏蛋白、N-钙黏蛋白、Stat3、Snail1、Slug、Twist1、Zeb1 和整合素α5)。对来自研究病例的 20 个新鲜 HCC 样本进行 EMT 标志物的基因表达定量实时聚合酶链反应 (PCR)。

结果

EMT 标志物的表达分别为 71%、25%、26%、27%、9%、4%、72%、47%、87%,对应的标志物为波形蛋白、E-钙黏蛋白、N-钙黏蛋白、Stat3、Snail1、Slug、Twist1、Zeb1 和整合素α5。HCC 组织中的 EMT mRNA 与蛋白表达相关 50-70%。在多变量分析中,波形蛋白是大肿瘤大小 (P=0.001)、高复发风险 (HRR) (P=0.006) 和无病生存时间较短 (P=0.03) 的独立预测因子。E-钙黏蛋白减少是 HRR 的预测因子 (P=0.002)。

结论

在预测复发方面,波形蛋白和 E-钙黏蛋白是 HCV 相关 HCC 中最强大的 EMT 预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28f5/9360938/b1ab117c3aad/APJCP-23-839-g001.jpg

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