锌转运体 ZIP4、ZIP14 和 ZnT9 在肝肿瘤发生中的表达——免疫组化研究。

Expression of zinc transporters ZIP4, ZIP14 and ZnT9 in hepatic carcinogenesis-An immunohistochemical study.

机构信息

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany; Medical Laboratory for Clinical Chemistry, Microbiology and Infectious Diseases "Prof. Schenk/Dr. Ansorge & Colleagues", Department Molecular Genetics, Schwiesaustr. 11, D-39124, Magdeburg, Germany.

Clinic of Gastroenterology, City Hospital Magdeburg, Klinikum Magdeburg GmbH, Birkenallee 34, D-39130, Magdeburg, Germany.

出版信息

J Trace Elem Med Biol. 2018 Sep;49:35-42. doi: 10.1016/j.jtemb.2018.04.034. Epub 2018 Apr 27.

DOI:10.1016/j.jtemb.2018.04.034

PMID:29895370

Abstract

INTRODUCTION

Dysregulation of both, systemic zinc levels and tissue-specific zinc transporters, is reported in chronic inflammatory and malignant liver disease (hepatocellular carcinoma, HCC). Aim of this study is to assess the expression level of three zinc transporters in liver tissue and HCC: ZIP4, ZIP14 and ZnT9.

METHODS

The study is based on tissue samples obtained from 138 patients with histologically proven HCC. Tissue specimens from tumor (n = 138) and extra-lesional specimens (n = 72) were assessed immunohistochemically for the expression of the three zinc transporters. Expression levels were semi-quantitatively scored and statistically analyzed with respect to the etiology of HCC (alcohol, AFLD; non-alcoholic fatty liver disease, NAFLD; virus-hepatitis, VH) and survival.

RESULTS

Overall, expression levels of ZIP4, ZIP14 and ZnT9 were significantly higher in HCC tissue than in adjacent extra-lesional liver tissue. Expression levels in tumor tissue and survival time revealed a negative correlation for ZIP4 and ZIP14, and in part for ZnT9 (nuclear staining) (p < 0.05), whereas cytoplasmic staining of ZnT9 did not correlate with survival. Furthermore, the expression level of ZIP4 in extra-lesional tissue showed inverse correlation with survival time.

CONCLUSION

The upregulation of zinc transporters in hepatic carcinogenesis and its negative correlation with survival time implies a regulatory/functional link between zinc-homeostasis and development/progression of HCC that deserves to be further explored.

摘要

简介

慢性炎症和恶性肝脏疾病（肝细胞癌，HCC）中报道了全身锌水平和组织特异性锌转运体的失调。本研究的目的是评估三种锌转运体在肝组织和 HCC 中的表达水平：ZIP4、ZIP14 和 ZnT9。

方法

该研究基于从 138 例经组织学证实的 HCC 患者获得的组织样本。对 138 例肿瘤组织（n=138）和非病变组织（n=72）标本进行免疫组织化学分析，以评估三种锌转运体的表达。表达水平进行半定量评分，并根据 HCC 的病因（酒精、AFLD；非酒精性脂肪性肝病、NAFLD；病毒性肝炎、VH）和生存率进行统计学分析。

结果

总体而言，ZIP4、ZIP14 和 ZnT9 在 HCC 组织中的表达水平明显高于相邻的非病变肝组织。肿瘤组织中的表达水平与生存时间呈负相关，ZIP4 和 ZIP14 呈负相关，部分 ZnT9（核染色）（p<0.05）呈负相关，而 ZnT9 的细胞质染色与生存时间无相关性。此外，非病变组织中 ZIP4 的表达水平与生存时间呈负相关。