The Correlation Between Trace Element Levels And Chemotherapeutic Sensitivity In Primary Liver Cancer

Objectives To investigate the distribution of trace elements(zinc, copper, manganese, and selenium) in cancer tissues, cancer-adjacent tissues, and cancerfree liver tissues of patients with primary liver cancer(PLC); and to explore whether the levels of trace elements in cancer tissues affect the chemotherapeutic drug sensitivity of cancer cells in PLC patients.Methods Serum samples were collected from healthy cases and PLC and patients with metastatic liver cancer(MLC) pre-operatively. Fresh cancer tissue, cancer-adjacent tissue, and cancer-free liver tissue samples were collected intra-operatively from PLC or MLC patients. The trace metal levels of tissue samples were analyzed by atomic absorption spectrophotometry. In vitro chemotherapeutic drug sensitivity of cancer cells was tested in PLC patients by methyl thiazolyl tetrazolium assay with 5-fluorouracil, doxorubicin, cisplatin, carboplatin, and mitomycin.Results Serum copper level in cancer patients(55 PLC, 12 MLC) was significantly lower than that of healthy cases(15 cases), there was no significant difference of serum copper level between PLC and MLC. Serum content of zinc, manganese and selenium were similar among cancer patients and healthy cases. In PLC and MLC patients, zinc, copper, manganese, and selenium had similar distribution gradients in liver tissues, generally increasing from cancer tissues to cancer-adjacent and cancer-free tissues with a significant difference. The zinc level of cancer tissues was significantly lower in MLC patients than in PLC patients(P=0.015). Except for zinc, the levels of trace elements tested in cancer tissues of PLC patients showed certain correlations with the values in other parts of liver tissue. In vitro drug sensitivity testing showed that the sensitivity of cancer cells to doxorubicin, cisplatin, carboplatin, and mitomycin was above 50%. With the correlation analysis, the carboplatin sensitivity of cancer cells was significantly negatively correlated with the selenium level of cancer tissues(r =-0.366,P = 0.044), the adriamycin sensitivity was negatively correlated with the manganese levels in cancer tissues(r=-0.497,P=0.004). With the partial correlation analysis, only the manganese content in cancer tissue is still negatively correlated with ADM efficacy(r=-0.450,P=0.014).Conclusions Serum copper level in cancer patients was significantly lower than that of healthy cases. In PLC patients, the zinc, copper, manganese and selenium levels were significantly lower in cancer tissues than in other parts of liver tissues; the selenium and manganese level of cancer tissues might affect the carboplatin or doxorubicin sensitivity of cancer cells.