DNA甲基转移酶在肝癌中的表达及其临床意义

Objective To investigate the expression of DNA methyltransferases (DNMTs) in liver cancer and its clinical significance. Methods The specimens of liver cancer tissues, adjacent tissues, cirrhotic tissues and chronic hepatitis tissues were collected from 50 patients who received radical resection at the First Affiliated Hospital of Sun Yat-Sen University from July 2007 to April 2008. The mRNA and protein expressions of DNMT1,DNMT3a and DNMT3b in liver cancer tissues, adjacent tissues, cirrhotic tissues and chronic hepatitis tissues were detected by real-time quantitative PCR and immunohistochemical staining. The mRNA expression of DNMTs in the liver cancer tissues was compared with those in the adjacent tissues, cirrhotic tissues and chronic hepatitis tissues by using t test and Mann-Whitney U test. The correlation between the protein expression of DNMTs in the liver cancer tissue and the clinicopathological features was analyzed by chi-square test or Fisher exact test, and the tumor-free survival time was analyzed by using Kaplan-Meier method and the difference in tumor-free survival rate between different patients was analyzed by Log-rank test. Results The mRNA expressions of DNMT1, DNMT3a and DNMT3b in the liver cancer tissue were 2.57, 2.29 and 4.86 times higher than those in the adjacent tissues (t = 3.94, 2. 72, 4. 06, P ＜ 0.05 ). The mRNA expressions of DNMT1, DNMT3a and DNMT3b were 2.38,2.14 and 4.66 times higher than those in the cirrhotic tissues, and 6.12, 4.58 and 12.99 times higher than those in the chronic hepatitis tissues. The mRNA expressions of DNMT1, DNMT3a and DNMT3b in the liver cancer tissue were significantly higher than those in the cirrhotic tissues and chronic hepatitis tissues ( U = 587.5,730. 0,562.5; 65.5, 64.5, 71.0, P ＜ 0.05). The protein expression of DNMT1 was correlated with the size, number,TNM stages and vascular invasion of tumors ( x2 = 4.08, 5.95, 4.08, P ＜ 0.05 ). The protein expression of DNMT3a was correlated with the size, number and TNM stages of tumors (x2 = 4.08, 5.95, 4.08, P ＜ 0.05 ).The mean tumor recurrence time of patients with low expressions of DNMT1 and DNMT3a were 9.4 and 8.7 months, which were significantly longer than 5.0 and 3.2 months of those with high expressions of DNMT1 and DNMT3a (x2 =3.89, 9.91, P＜0.05). Conclusions DNMTs play an important role in hepatocarcinogenesis.High expressions of DNMT1 and DNMT3a are correlated with the postoperative recurrence of liver cancer, which are valuable prognostic factors for liver cancer.

Expression of DNA methyltransferases in liver cancer and its clinical significance