Clinical significance of aberrant cyclin-dependent kinase-like 2 methylation in hepatocellular carcinoma.

BACKGROUND AND AIMS:Aberrant DNA methylation of cyclin-dependent kinase-like 2 (CDKL2) had been observed in several types of tumors. Herein, the present study was aimed to explore the epigenetic and expression status of CDKL2 and evaluate the diagnostic potential of CDKL2 methylation in hepatocellular carcinoma (HCC). METHODS:The methylation status of CDKL2 was detected by methylation-sensitive restriction enzyme based quantitative PCR (MSRE-qPCR) and bisulfite genomic sequencing (BGS). The mRNA expression of CDKL2 was measured using real-time quantitative PCR (qPCR). The correlations between the methylation of CDKL2 and mRNA expression, clinicopathological features were evaluated. RESULTS:Compared with normal liver tissues, the methylation levels of CDKL2 were significantly increased in the HCC tissues and cell lines (All p < 0.05). And the receiver operating characteristic (ROC) analysis showed that the hypermethylation of CDKL2 had a high specificity and sensitivity to distinguish adjacent non-tumor tissues from HCC tissues. Additionally, the mRNA expression levels of CDKL2 were decreased both in HCC tissues and cell lines than those in normal liver tissues (All p < 0.05), and the expression could be upregulated by 5-aza-2'-deoxycytidine treatment in HCC cell lines. Furthermore, the methylation of CDKL2 was negatively correlated with its mRNA expression (p < 0.001, r_s = -0.513), and was associated with gender (p = 0.023), age (p = 0.001) and tumor size (p = 0.016). CONCLUSIONS:Our results showed that CDKL2 promoter hypermethylation played an important role in hepatocarcinogenesis and might be a valuable biomarker for HCC diagnosis.

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