The innovative regularity and role of p16 methylation in blood during HCC development.

Purpose: This study was performed to examine the regularity and role of p16 methylation in hepatocellular carcinoma (HCC) blood. Methods: Big data of the case-control studies due to blood p16 methylation detection were collected in English and Chinese Journals. The risk of HCC's histologic process was investigated using both Meta-analysis and the quantitative correlation analysis. Results: p16 methylation frequencies in blood were gradually increased from 0 % in normal to 10 % in benign disease, and to 60 % in HCC development. Based on p16 methylation of normal control blood, p16 methylation between normal and benign disease had no risk, and the methylation risk in HCC was significantly increased from normal to HCC through benign disease OR, 95% CI =16.23 ( 11.66, 22.58 ). Compared with the benign disease matched by HCC patient, the methylation risk of p16 in HCC was found, with the pooled OR value of 10.06 (95% IC = 7.64, 13.21) in blood. In addition, the regulatory mechanism affecting p16 methylation risk in normal blood had no role, and the strength of p16 methylation risk was rapidly increased between benign diseases and HCC blood. p16 methylation risk started from the patients with benign disease in blood. These results in blood and tissue detection were basically consistent. Conclusions: HCC pathogenesis affecting p16 methylation don't work during normal blood, when from benign diseases to HCC bloods, can produce powerful role. The transcriptional inactivation associated with p16 methylation might start from benign liver disease, and might be increased from benign liver disease to HCC process. p16 methylation in blood can be used as a promising non-invasive biomarker to HCC's prediction and diagnosis.