Hui Zhang, Wanpin Nie, Feizhou Huang
Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland)
Med Sci Monit 2015; 21:3077-3082
Primary liver cancer is a common malignant tumor that causes serious damage to human health. DNA methylation is common in epigenetics. DNA methylation plays an important role in the process of primary liver cancer occurrence and development. The P14ARF gene is an important tumor suppressor gene. It was found that P14ARF methylation is associated with the degree of malignancy in multiple tumors. Therefore, this study aimed to investigate the relationship between P14ARF methylation level and primary liver cancer malignant degree.
MATERIAL AND METHODS: Carcinoma tissues and adjacent tissues were collected from 87 primary liver cancer patients. Pyrosequencing was applied to obtain P14ARF methylation. Real-time PCR was used to detect P14ARF mRNA level.
RESULTS: P14ARF methylation level in cancerous tissue was significantly higher than in the adjacent tissue (t=76.54, P<0.001). P14ARF methylation showed no significant difference in patients with different age, sex, smoking status, or drinking status. It did not present an obvious difference in tumors with different size. Its methylation level increased following the improvement of TNM stage (P<0.05). Compared with the adjacent tissue, P14ARF mRNA in carcinoma tissue decreased by 31% (t=28.91, P<0.001). P14ARF methylation showed a significant negative correlation with mRNA expression in cancerous tissue (r=–0.43, P<0.01).
CONCLUSIONS: P14ARF mRNA level is regulated by DNA methylation in primary liver cancer. P14ARF gene DNA methylation may be associated with the occurrence of primary liver cancer occurrence and TNM staging.
Keywords: Carcinoma - genetics, Cyclin-Dependent Kinase Inhibitor p16 - genetics, DNA Methylation, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Liver Neoplasms - genetics, Prognosis, RNA, Messenger - metabolism, Real-Time Polymerase Chain Reaction, Sarcoglycanopathies - pathology, Sequence Analysis, DNA, Tumor Suppressor Protein p14ARF - genetics