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

Abstract

ObjectivesZinc 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. MethodsThis 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. ResultsZNT1 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.