Copper Chaperone for Superoxide Dismutase Expression is Down-Regulated and Correlated with More Malignant Tumoral Features and Poor Prognosis in Human Hepatocellular Carcinoma

Background: Up-regulated expression of copper chaperone for superoxide dismutase (CCS) is identified in a multitude of tumors and is closely related to more malignant tumoral biological behaviors. However, little is known about the role of CCS in hepatocellular carcinoma (HCC). This study aims to explore the expression pattern and the significance of CCS in human HCC.Methods: Fresh samples of HCC with paired adjacent tissues were obtained from 32 patients who underwent hepatectomy. The expression levels of CCS and representative malignant biomarkers in HCC were investigated by western blotting and immunohistochemistry staining, respectively. The correlation between the expression status of CCS and the activities of selected malignant biomarkers and important drive genes of HCC oncogenesis, patient’s clinicopathological features and prognosis, were analyzed. Additional bioinformatics investigation of dataset retrieved from database were performed to further explore the role of CCS in human HCC. Results: The majority of the HCC tumor (78.1%, 25/32) presented a lower expression of CCS, whereas in the minority of the tumor (22.9%, 7/32) the expression of CCS was determined as higher. Furthermore, it was found that the expression level of CCS was significantly correlated with malignant biomarkers. The expression of CCS was reversely correlated with ES grade and TNM stage to some extent. And there is a significant correlation between the CCS gene and a series of genes in the development and progression of HCC. Patients with higher CCS expression level were prone to have a better prognosis. Conclusion: HCC presented a unique lower expression pattern of CCS which reversely correlated with the more malignant tumoral features and poor prognosis.