[Correlations of CpG island methylator phenotype and OPCML gene methylation to carcinogenesis of hepatocellular carcinoma].
OBJECTIVE
CpG island methylator phenotype (CIMP) is cancer-specific and involves in the promoter hypermethylation of multiple genes. It is correlated to the genesis or prognosis of various tumors, but it has rarely been reported in hepatocellular carcinoma (HCC). OPCML (opioid-binding protein/cell adhesion molecule-like) gene has been studied mainly in epithelial ovarian cancer, and is thought to be a candidate tumor suppressor gene in epithelial ovarian cancer. This study was to explore the correlations of CIMP and OPCML gene expression to the carcinogenesis of HCC.


METHODS
The methylation status of OPCML, p15, SOCS-1, GST-p, RAR-b, p16, p73, p14, MGMT, hMLH1 in 50 specimens of HCC and pericancer tissues was detected using methylation-specific polymerase chain reaction (MSP).


RESULTS
The hypermethylation rates of genes were higher in HCC than in pericancer tissues [OPCML (70.0% vs. 64.6%), p15 (58.0% vs. 50.0%), SOCS-1 (78.0% vs. 50.0%), GST-p (56.0% vs. 27.1%), RAR-b (30.0% vs. 6.3%), p16 (26.0% vs. 14.6%), p73 (16.0% vs. 0%), p14 (36.0 vs. 27.1%), MGMT (16.0% vs. 10.4%), and hMLH1 (18.0% vs. 4.2%)]. The methylation rates of SOCS-1, GST-p, RAR-b, p16 and p73 were significantly higher in HCC than in adjacent non-neoplastic tissues (P<0.05). The recurrence occurred earlier in CIMP-positive group (> or =3 methylated genes) than in CIMP-negative group (<3 methylated genes)(P<0.05). The 1-year disease-freely survival rate was significantly lower in CIMP-positive group than in CIMP-negative group (18.2% vs. 75.0%, P<0.05).


CONCLUSIONS
CIMP exists in HCC, and may be a prognostic factor of HCC. Promoter methylation of OPCML gene may play an important role in hepatocarcinogenesis.
Liu
Wen-Ji
WJ
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, P. R. China.
Wang
Li
L
Wang
Jian-Ping
JP
Li
Jin-Qing
JQ
Zhang
Chang-Qin
CQ
Zheng
Lie
L
Yuan
Yun-Fei
YF
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D058851:GPI-Linked Proteins; D052138:Genes, Neoplasm; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010641:Phenotype; D015996:Survival Rate
D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; C059785:OPCML protein, human