Detecting abnormal methylation of tumor suppressor genes GSTP1, P16, RIZ1, and RASSF1A in hepatocellular carcinoma and its clinical significance

Zhen Qu; Yong Jiang; Huan Li; DE-Cai Yu; Yi-Tao Ding

doi:10.3892/ol.2015.3536

Detecting abnormal methylation of tumor suppressor genes GSTP1, P16, RIZ1, and RASSF1A in hepatocellular carcinoma and its clinical significance

Oncol Lett. 2015 Oct;10(4):2553-2558. doi: 10.3892/ol.2015.3536. Epub 2015 Jul 24.

Authors

Zhen Qu¹, Yong Jiang², Huan Li², DE-Cai Yu¹, Yi-Tao Ding¹

Affiliations

¹ Department of Hepatobiliary Surgery, Drum Tower Hospital, Medicine School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
² Department of Hepatobiliary Surgery, Changzhou First People's Hospital, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.

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, and RASSF1A, 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 of RIZ1 and GSTP1 genes 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 of P16 and RASSF1A genes 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 the GSTP1 gene in tumors with capsular invasion was significantly increased compared with that in tumors without capsular invasion (P<0.05). The methylation frequency of P16 gene 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 of RIZ1 and RASSF1A genes was not significantly correlated with the clinicopathological data (P>0.05). Previous studies have demonstrated that the methylation status of RIZ1 and GSTP1 genes is HCC-specific, and thus may be used as a biomarker to assist the clinical diagnosis of HCC. While the methylation of GSTP1 gene promoter may associate with the invasiveness of HCC, chronic hepatitis B virus infection may be the cause of methylation-induced P16 inactivation.

Keywords: hepatocellular carcinoma; methylation; suppressor gene.