NRSF/REST levels are decreased in cholangiocellular carcinoma but not hepatocellular carcinoma compared with normal liver tissues: A tissue microarray study

Abstract

The transcription factor neuron-restrictive silencer factor (NRSF), also termed repressor element 1-silencing transcription factor (REST), has been previously demonstrated to repress the expression of neuronal genes in non-neuronal cells, facilitating the controlled development and organization of nerve tissue. However, previous studies have reported NRSF/REST to be upregulated or downregulated in multiple types of carcinoma. Liver diseases are a major global health concern, with cirrhosis and liver carcinoma among the most common causes of mortality worldwide. A previous study demonstrated that there were >400 NRSF/REST target genes in mouse liver cells; however, the expression profile of NRSF/REST in human liver disease remains unclear. The present study examined NRSF/REST expression in human normal and liver carcinoma samples using tissue microarray immunohistochemistry. The results demonstrated that in normal liver tissues, NRSF/REST can be detected in the cytoplasm and nuclei of the cell; whereas in the liver carcinoma tissue, NRSF/REST is only detected in the cytoplasm. Furthermore, the number of samples with high levels of NRSF/REST was significantly lower in cholangiocellular carcinoma samples compared with normal tissues. Additionally, no detectable sex- or age-associated differences were identified in NRSF/REST expression among all the tissues examined. In conclusion, the results of the present study revealed nuclear loss of NRSF/REST in hepatic carcinomas and decreased expression of NRSF/REST in cholangiocellular carcinoma, indicating that the cytoplasmic translocation of NRSF/REST may be involved in liver tumorigenesis. A low expression level of NRSF/REST may be a novel biomarker for cholangiocellular carcinoma.