title: Detecting abnormal methylation of tumor suppressor genesGSTP1,P16,RIZ1, andRASSF1Ain hepatocellular carcinoma and its clinical significance.
abstract: Hepatocellular carcinoma (HCC) has a high rate of mortality. Further studies into epigenetic changes in HCC, particularly the abnormal methylation of tumor suppressor genes (TSGs), are required, since these changes may provide novel biomarkers for early screening and diagnosis of HCC. By using methylation-specific polymerase chain reaction (MSP), the present study detected the methylation status in the promoter region of 4 candidate TSGs,GSTP1, P16, RIZ1, andRASSF1A, respectively, in 35 paired HCC and tumor-adjacent liver tissues in addition to 20 normal liver tissues. Their effect on the initiation and progression of HCC was also investigated by analyzing the clinicopathological data. The results of the present study revealed that the methylation level ofRIZ1andGSTP1genes in HCC was significantly increased compared with that in the adjacent tissues (P<0.01) and the normal liver tissues (P<0.01). The methylation frequency ofP16andRASSF1Agenes was not significantly increased compared with that observed in the adjacent tissues (P>0.05) but was significantly increased compared with the normal tissues (P<0.01). In HCC tissues, the methylation frequency of theGSTP1gene in tumors with capsular invasion was significantly increased compared with that in tumors without capsular invasion (P<0.05). The methylation frequency ofP16gene in hepatitis B surface antigen (HbsAg)-positive HCC patients was significantly increased compared with that in HbsAg-negative patients (P<0.05). The methylation status ofRIZ1andRASSF1Agenes was not significantly correlated with the clinicopathological data (P>0.05). Previous studies have demonstrated that the methylation status ofRIZ1andGSTP1genes is HCC-specific, and thus may be used as a biomarker to assist the clinical diagnosis of HCC. While the methylation ofGSTP1gene promoter may associate with the invasiveness of HCC, chronic hepatitis B virus infection may be the cause of methylation-inducedP16inactivation.
authors.affiliation: Department of Hepatobiliary Surgery, Drum Tower Hospital, Medicine School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Department of Hepatobiliary Surgery, Changzhou First People's Hospital, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, Changzhou First People's Hospital, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, Drum Tower Hospital, Medicine School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: DE-Cai
authors.initials: DC
authors.lastname: Yu
authors.affiliation: Department of Hepatobiliary Surgery, Drum Tower Hospital, Medicine School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Ding
keywords: hepatocellular carcinoma; methylation; suppressor gene