Laura Gartmann1, Thomas Wex1, Kurt Grüngreiff2, Dirk Reinhold3, Thomas Kalinski4, Peter Malfertheiner5, Kerstin Schütte6. 1. 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. 2. Clinic of Gastroenterology, City Hospital Magdeburg, Klinikum Magdeburg GmbH, Birkenallee 34, D-39130, Magdeburg, Germany. 3. Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany. 4. Institute of Pathology, Otto-von-Guericke University, Leipziger Str. 44, D-39120, Magdeburg, Germany. 5. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany. 6. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany; Department of Internal Medicine and Gastroenterology, Niels-Stensen-Kliniken, Marienhospital Osnabrück GmbH, Bischofsstraße 1, D-49074, Osnabrück, Germany. Electronic address: kerstin.schuette@niels-stensen-kliniken.de.
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.
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.
Authors: Alexander Scheiter; Katja Evert; Lucas Reibenspies; Antonio Cigliano; Katharina Annweiler; Karolina Müller; Laura-Maria-Giovanna Pöhmerer; Hongwei Xu; Guofei Cui; Timo Itzel; Silvia Materna-Reichelt; Andrea Coluccio; Kamran Honarnejad; Andreas Teufel; Christoph Brochhausen; Frank Dombrowski; Xin Chen; Matthias Evert; Diego F Calvisi; Kirsten Utpatel Journal: Mol Oncol Date: 2021-11-20 Impact factor: 7.449