Hypermethylation Of FHIT, CDH13, CRBP1 And LKB1 Genes In Hepatocellular Carcinoma

Objective To study the methylation of FHIT, CDH13, CRBP1 and LKB1 genes in hepatocellular carcinoma (HCC). Methods The methylation of the genes were detected by the methylation specific PCR (MSP) method in 45 patients with HCC (tumoral and peritumoral tissue), 14 cases of normal livers and 4 HCC cell lines (SK-Hep-1, Hep-G2, Hep-3B and Huh7). The relationship between the frequency of methylation of the genes and clinicopathological features were analyzed. Results The frequencies of methylation of FHIT, CDH13, CRBP1 and LKB1 in tumoral tissue were 71.1%(32/45), 42.2%(19/45), 31.1%(14/45) and 2.2%(1/45), respectively. In the paired peritumoral tissues, the frequencies of methylation of FHIT, CDH13, CRBP1 and LKB1 were 64.4 % (29/45), 37.8 % (17/45), 13.3 % (6/45) and 0 % (0/45), respectively. in nomal livers were 14.3%(2/14), 14.3%(2/14), 0%(0/14) and 0%(0/14), respectively. Regarding HCC cell lines, the promoter regions of FHIT, CDH13, CRBP1 and LKB1 were methylated in three (75.0%), one (25.0%), two (50.0%) and none out of 4 samples, respectively. The methylation of at least one gene could be detected in 88.9% (40/45) tumoral tissues and 84.4% (38/45) peritumoral tissues. There is no statistical difference between tumoral tissues and peritumoral tissues. At least one of the four genes was methylated in 28.6%(4/14) samples with normal liver tissues. The proportion were lower than in tumoral tissues (P=0.0000) and peritumoral tissues (P=0.0001). The samples of two genes methylation in tumoral and peritumoral tissues were 15 (33.3%) and 14(31.1%), respectively. The proportion...