Correlation of CpG island methylator phenotype with poor prognosis in hepatocellular carcinoma.
CpG island methylator phenotype (CIMP), in which multiple genes are concurrently methylated, is an important mechanism in hepatocellular carcinoma development. We determined a hypermethylation profile in hepatocellular carcinoma (HCC). We examined the promoter methylation status of 10 genes in 60 cases of hepatocellular carcinoma (HCC), 60 cases of paired non-tumor tissues, and 6 cases of normal tissues by methylation-specific PCR. The average methylated gene numbers were significantly different between HCC and nontumor tissues (p<0.001). We found metastasis, gamma-glutamyl transpeptidase (GGT) and tumor node metastasis (TNM) stage were significantly different among patients with different CIMP status. Patients with high frequency CIMP tumors had significantly worse survival than patients with intermediate frequency or no CIMP tumors (p<0.01 and p<0.05, respectively). Our results suggested that CIMP could serve as a molecular marker of late stage and poorly prognostic HCC development.
Cheng
Yue
Y
Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, China.
Zhang
Changsong
C
Zhao
Jun
J
Wang
Chenyang
C
Xu
Yun
Y
Han
Zhipeng
Z
Jiang
Guocheng
G
Guo
Xianling
X
Li
Rong
R
Bu
Xinxin
X
Wu
Mengchao
M
Wei
Lixin
L
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010641:Phenotype; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015996:Survival Rate; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D005723:gamma-Glutamyltransferase