Zinc transporter 1 expression in hepatocellular carcinoma correlates with prognosis: A single-center retrospective study

Naruyasu Kakita; Kazuhiro Katayama; Toshimitsu Yasui; Shin Satake; Kenji Aoi; Hisashi Jo; Yong Kook Kim; Masaru Yamazaki; Ayako Hashimoto; Taiho Kambe

doi:10.1016/j.jtemb.2023.127354

Zinc transporter 1 expression in hepatocellular carcinoma correlates with prognosis: A single-center retrospective study

J Trace Elem Med Biol. 2024 Mar:82:127354. doi: 10.1016/j.jtemb.2023.127354. Epub 2023 Dec 6.

Authors

Affiliations

¹ Department of Gastroenterology and Hepatology, Kaizuka City Hospital, 3-10-20 Hori, Kaizuka city, Osaka 5970015, Japan. Electronic address: n.kakita@hosp.kaizuka.osaka.jp.
² Department of Gastroenterology and Hepatology, Kaizuka City Hospital, 3-10-20 Hori, Kaizuka city, Osaka 5970015, Japan.
³ Department of Surgery, Kaizuka City Hospital, 3-10-20 Hori, Kaizuka city, Osaka 5970015, Japan.
⁴ Department of Pathology, Kaizuka City Hospital, 3-10-20 Hori, Kaizuka city, Osaka 5970015, Japan.
⁵ Department of Food and Nutrition, Faculty of Home Economics, Kyoto Women's University, 544 Kamiumamachi, Higasiyamaku, Kyoto city, Kyoto 6050927, Japan.
⁶ Graduate School of Biostudies, Kyoto University, Yoshidahonmachi, Sakyoku, Kyoto city, Kyoto 6068501, Japan.

PMID: 38103516
DOI: 10.1016/j.jtemb.2023.127354

Abstract

Objectives: Zinc is crucial in the pathogenesis of hepatocellular carcinoma; however, no reports have examined its association with clinical parameters and zinc transporter 1 (ZNT1) expression intensity. This study aimed to assess the association between ZNT1 expression and prognosis in patients with hepatocellular carcinoma.

Methods: This retrospective study included 65 patients who underwent surgical hepatocellular carcinoma resection at a single center between January 2011 and June 2015. ZNT1 expression on hepatocellular carcinoma cells from specimens was assessed using immunohistochemistry, and the relationship between its intensity and various clinical indexes was examined with univariate and multivariable analyses and the Mann-Whitney U, Kruskal-Wallis, Bonferroni, and log-rank tests.

Results: ZNT1 expression on the hepatocellular carcinoma cell membrane was negative in 31 patients and positive in 34 patients, including nine patients showing strongly positive expression. Patients with and without ZNT1 expression had similar blood zinc concentrations, α-fetoprotein levels, protein induced by vitamin K absence-antagonist-II levels, gross classification, maximal tumor diameters, and background liver disease. The blood zinc concentrations were significantly lower in patients with strongly positive ZNT1 expression (57.0 ± 22.1 μg/dL) than in those with positive ZNT1 expression (71.1 ± 14.2 μg/dL; P = 0.015) or those with no ZNT1 expression (72.9 ± 14.1 μg/dL; P = 0.043). Overall survival was significantly shorter in ZNT1-expressing patients than in non-expressing patients (log-rank test, P = 0.024). Multivariable analysis using the Cox proportional hazards model identified maximal tumor diameter (hazard ratio, 1.018; 95% confidence interval, 1.002-1.034; P = 0.026) and ZNT1 expression status (hazard ratio, 2.082; 95% confidence interval, 1.196-3.621; P = 0.010) as prognostic contributing factors.

Keywords: Hepatocellular carcinoma; Immunohistochemistry; Prognostic factor; Surgical resection; Zinc metabolism.

MeSH terms

Carcinoma, Hepatocellular*
Humans
Liver Neoplasms*
Retrospective Studies
Zinc / metabolism

Substances

Zinc
zinc-binding protein
SLC30A1 protein, human