Serum zinc level and tissue ZIP4 expression are related to the prognosis of patients with stages I–III colon cancer

BACKGROUND: It has been reported that serum Zinc (Zn) and tissue ZRT, IRT-like protein 4 (ZIP4) are involved in the oncogenesis of several cancers. However, the relationship between them and the prognosis of colon cancer is unclear. METHODS: This was a prospective study including 116 patients with stages I–III colon cancer. The level of serum Zn was measured using a flame atomic absorption spectrometer. The expressions of ZIP4 in cancer tissues were measured using western blot and normal colon tissues from healthy volunteers were used as a control. The primary outcome was 2-year survival and secondary outcomes included the incidences of locoregional recurrence and distant metastasis. RESULTS: The average level of serum Zn in participants was 856.0±322.5 µg/L. Kaplan-Meier survival curves showed that patients with Zn <856.0 µg/L had a significantly higher incidence of distant metastasis (P=0.02) and a significantly lower survival rate than those with Zn ≥856.0 µg/L (P=0.005). Multivariate logistic regression analysis also confirmed that having level Zn <856.0 µg/L was risk factor for the two outcomes. The expression of ZIP4 in cancer tissues was greatly increased as compared with the healthy control, with an average fold change of 2.4. The level of serum Zn was found to be positively correlated with the expression of ZIP4 in tissue. Multivariate logistic regression analysis indicated that increased expression of tissue ZIP4 was an important risk factor for locoregional recurrence (P=0.032), distant metastasis (P=0.039), and overall survival (P=0.035). CONCLUSIONS: Both lower levels of serum Zn and increased expression of ZIP4 in tissue are associated with a poorer prognosis of patients with stages I–III colon cancer.