The Study Of WIF-1 Methylation And Expression In Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common life-threatening malignancies in the world with a high mortality and morbility. Carcinogenesis and development of HCC is a complicated process with multiple gene participated and multiple phase developed, and the molecular mechanism of hepatocarcinogenesis remains unclear. Aberrant methylation of tumor suppressor genes is an important reason of tumorigenesis.So, we selected WIF-1 gene as a target for testing the methylation and expression level in tissue samples and estimating their clinical significance.AIM:To investigate the level of promoter methylation and geneexpression of WIF-1 in hepatocellular carcinoma. To estimate the value of aberrant methylation and expression of WIF-1 as a biomarkerfor diagnosis and prognosis of HCC.METHODS:We collected 53 tumor and adjacent non-tumor tissuesamples, and tested methylation status of WIF-1 in these samples quantitatively by quantitative methylation specific polymerase chain reaction (Q-MSP).The expression of WIF-1 was determined by quantitative real-time reverse transcriptase PCR (Q-RT-PCR). Then we investigated the correlation among methylation status, mRNA expression, and clinicopathological data.RESULTS:The results of Q-MSP analysis indicated that the methylation of WIF-1 in HCC increased significantly compared with adjacent non-tumor tissues(P< 0.001).ROC analysis demonstrated methylation of WIF-1 could distinguish the tumor lesions from non-malignant tissuesefficiently (AUC=0.714, P<0.001).The methylation of WIF-1 had no significant correlation with patients gender, age, tumor number, liver cirrhosis status, Child-pugh grade, and TNM stage(P>0.05). Kaplan-Meier survival analysis showed the patients with lower methylation had a better disease-free survival time(P<0.05).The analysis of Q-RT-PCR showed that normal liver tissues had a significantly higher expression of WIF-1 than other kinds of tissues except for chronic hepatitis tissues.Tumor tissues compared with adjacent non-tumor tissueshad a lower expression level of WIF-1(P<0.05).Among 53 HCCs and their corresponding nontumorous liver tissues, the prominent down-regulation of WIF-1 (by>2-fold) was observed in 31 of 53 HCCs compared with nontumorous liver tissues.The number of samples with prominent down-regulation were 11(55.0%) in aberrant hypermethylated HCCs and 20(60.6%) in the tumor samples without hypermethylation, respectively.CONCLUSION:The promoter hypermethylation of WIF-1 is a common event in HCC and may plays an important role at the stage of hepatocarcinogenesis, and the methylation level of WIF-1 may server as a potential biomarker for diagnosis and prognosis of HCC. WIF-1 methylation and other factors mediated the expression of WIF-1.