Clinical significance of aberrant DEUP1 promoter methylation in hepatocellular carcinoma

Oncol Lett. 2019 Aug;18(2):1356-1364. doi: 10.3892/ol.2019.10421. Epub 2019 May 30.

Abstract

Accumulating studies have shown that methylation of tumor suppressor genes plays an important role in tumorigenesis. Deuterosome assembly protein 1 (DEUP1) has been implicated as a suppressor gene in some tumors and promoter methylation led to silencing of its expression. However, the roles of DEUP1 promoter methylation and expression in hepatocellular carcinoma (HCC) are not clear. In the present study, the expression and methylation of the DEUP1 promoter in HCC was investigated and the correlations with HCC occurrence and development were explored. A total of 60 HCC tumor and adjacent non-tumor tissues were included in this study. Reverse transcription-polymerase chain reaction, bisulfite PCR sequencing, immunohistochemistry and western blotting were applied to detect the methylation status of the DEUP1 promoter and its expression, and to analyze their associations with clinicopathological data. The results showed that the mRNA and protein expression of DEUP1 in adjacent non-tumor tissues was significantly increased compared with in the HCC tissues. DEUP1 promoter methylation was detected in 46/60 (76.7%) tumor tissues and there was a negative correlation between promoter methylation and DEUP1 protein expression (P<0.05). Analysis of the clinicopathological data revealed that the mRNA and protein expression of DEUP1, and its promoter methylation status, was associated with tumor node metastasis stage and tumor differentiation. Taken together, the results of the present study suggested that methylation of the DEUP1 promoter maybe an important mechanism for gene inactivation and has a critical role in the occurrence and development of liver cancer.

Keywords: bisulfite PCR sequencing; deuterosome assembly protein 1; hepatocellular carcinoma; methylation; tumor suppressor gene.