Analysis of metalothionein in patients with malignant liver tumors.

Abstract

Background: Malignant liver tumors are highly aggressive with a poor prognosis. Metalothionein (MT) is a low-molecular intracellular protein, whose primary function is to regulate the homeostasis of heavy metals in many organisms. There are only few studies focusing on the molecular mechanisms of MT expression. Recent studies show its significant relations to carcinogenesis, spontaneous mutagenesis and efficiency of antitumor medicine. In previous studies, the increase of MT levels in cancer patients was proven. The aim of this work is to study MT as well as to increase the efficiency of malignant liver tumor diagnosis.

Methods: In our pilot study (2022-2023) we observed a group of 15 patients with hepatocellular carcinoma (diagnosis C220) and a group of 15 patients with hepatoblastoma (diagnosis C222). The control group included 20 healthy probands. We developed our own modified method for the analysis. Blood serum samples of the probands were denaturated (99 ˚C, 20 min). MT was determined by an electrochemical method. Obtained data were stored and processed in the laboratory information system QINSLAB.

Results: In denaturated blood serum samples, we obtained voltametric curves of MT. We determined concentrations of MT by evaluating the area under the curve (AUC). To differentiate normal and abnormal concentrations of MT, blood samples of healthy probands were used (N = 20), with the average MT levels of 2.0 ± 1.3 µg/L and median 1.9 µg/L. In patients diagnosed with HCC, the average MT levels were 9.1 ± 6.5 µg/L and median 9.0 µg/L. The receiver operating characteristic (ROC) analysis showed AUC 0.864 (95% CI 0.736-0.992), sensitivity 0.74 and specificity 0.75. In patients diagnosed with hepatoblastoma, the average MT concentrations measured were 11.5 ± 7.5 µg/L and the median was 10.9 µg/L. The ROC analysis displayed AUC 0.868 (95% CI 0.751-0.993), sensitivity 0.84 and specificity 0.86. The correlation analysis showed correlation between MT and carcinoembryonic antigen (CEA) (r = 0.99), uric acid (r = -0.86) and potassium ions (r = -0.94).

Conclusion: In this pilot study, we observed the association of MT levels in healthy probands and malignant liver tumor patients. Many previous studies show that MT concentrations are increasing as the illness progresses. We assume that this increase is connected to the high metabolic activity of cancer cells. This study will continue with collecting a larger number of samples.