The association between methylation patterns of DNAH17 and clinicopathological factors in hepatocellular carcinoma

The aim of the study was to explore the correlation between the methylation status of DNAH17 and HCC. Our findings suggested that aberrant methylation of DNAH17 might contribute to hepatocarcinogenesis and progression and could be a promising biomarker for tumor thrombosis in HCC patients.

Abstract

Background

Hepatocellular carcinoma (HCC) is a malignancy with poor prognosis. Complex genetic and epigenetic alterations are the two primary causes of HCC. The aim of the study was mainly to explore the correlation between the methylation status of DNAH17 and HCC.

Methods

We evaluated the methylation levels of DNAH17 in 163 HCC samples and their paired normal tissue using Sequenom EpiTYPER assays and performed the TaqMan copy number assay to assess the copy number status of DNAH17 in HCC samples.

Results

The mean methylation levels were significantly decreased in the tumor tissues compared to the paired normal tissues in both selected regions of DNAH17 (amplicon 1:58.7% vs 84.5%, P < 0.0001; amplicon 2:69.9% vs 84.5%, P = 0.0060). Contrarily，both RNA‐seq and immunohistochemistry indicated the expression of DNAH17 was increased in tumor tissues (P < 0.05). DNMT inhibitor decitabine treatment could increase the expression of DNAH17 in HCC cell lines. DNAH17 gene amplification always companied with hypomethylation status. Moreover, hypomethylation status was associated with several clinical characteristics, such as male patients, higher AFP values, higher age of onset, fibrous capsules, tumor necrosis, liver cirrhosis, and tumor thrombus (P < 0.05). Receiver operator characteristic (ROC) curve analysis demonstrated the methylation levels of DNAH17 could efficiently predict the existence of the fibrous capsule (AUC = 0.695) and tumor thrombus (AUC = 0.806).

Conclusions

These findings suggested that aberrant methylation of DNAH17 was associated with comprehensive HCC clinicopathological factors and could be a promising biomarker for tumor thrombosis in HCC patients.

http://bit.ly/2V3WV3U