Abstract
TRIM58 (tripartite motif containing 58) has been reported as a novel methylated gene in hepatocellular carcinoma (HCC) by methylation microarrays. However, its associations with mRNA expression and clinicopathological characteristics have not been evaluated. In this study, we explored the potential clinical implications of TRIM58 methylation in HCC. We analyzed the methylation level of TRIM58 in 181HCC tissues, 172matched adjacent non-tumor tissues and 13normal liver tissues using methylation-sensitive restriction enzyme based quantitative PCR and bisulfite genomic sequencing. Further, the mRNA expression level of TRIM58 was measured in 46paired HCC and adjacent non-tumor tissues by quantitative real-time PCR. Moreover, the relationship between TRIM58 methylation and mRNA expression, the clinicopathological features, as well as prognostic value were evaluated. The results showed that TRIM58 methylation was significantly higher in HCC tissues compared with adjacent non-tumor tissues and normal liver tissues (both p<0.0001). Using 10% as the cut-off value, hypermethylation of TRIM58 was specific in HCC tissues (28.18%, 51/181), with a tendency to correlate with unfavorable disease-free survival (p=0.047). Moreover, TRIM58 expression was significantly decreased in HCC tissues compared with adjacent non-tumor tissues (p<0.0001), and showed a negative association with DNA methylation (p=0.015, rs=-0.260). Our data indicate that TRIM58 methylation is a common event in HCC and may contribute to downregulation of its mRNA expression. Furthermore, hypermethylation of TRIM58 tends to be associated with worse DFS after hepatectomy. However, the potential clinical application of TRIM58 need to be further investigated.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignancies worldwide [1]
To investigate the methylation status of TRIM58 in HCC, we firstly evaluated the methylation level in 30 paired HCC tissues and adjacent non-tumor tissues using Bisulfite genomic sequencing (BGS)
TRIM58 methylation was first reported in HCC by methylation microarrays, and validated in only 10 paired primary tumor and adjacent liver tissues [13]
Summary
Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignancies worldwide [1]. The major risk factors contributing to HCC include infection with hepatitis B or C virus, non-alcoholic steatohepatitis disease, aflatoxin B exposure and chronic alcoholism [2,3]. DNA methylation, the best-characterized epigenetic mechanism, has been reported as one of the pivotal alterations in HCC development and progression [7,8]. Global genomic hypomethylation and gene specific hypermethylation are two main patterns of aberrant DNA methylation, and these alterations coexist in HCC. Growing evidence showed that aberrant methylation presents potential clinical applications for HCC detection, diagnosis and prognosis [9,10].
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