Abstract
BackgroundTo evaluate the promoter methylation status of MUC2 gene and mRNA expression in patients with hepatocellular carcinoma.MethodsWe analyzed MUC2 methylation by MSP, and MUC2 mRNA by real-time PCR in 74 HCC.ResultsMUC2 mRNA were lower in HCC tissues (Mean -ΔCt = −4.70) than that in Non-HCC tissues (Mean -ΔCt = −2.98). Expression of MUC2 was elevated in only 23 (31.08%) of the 74 HCC patients. MUC2 promoter was hypermethylated in 62.2% (46/74) of HCCs, and in only 18.9% (14/74) of non-tumor samples. MUC2 mRNA were lower in HCC patients with hypermethylation (Mean -ΔΔCt = −2.25) than those with demethylation (Mean -ΔΔCt = −0.22), and there is a decreased tendency for MUC2 mRNA in HCC patients with promoter hypermethylation (p = 0.011). There was a significantly correlation found between MUC2 mRNA and HBV and AFP in HCC. The loss of MUC2 mRNA and hypermethylation could be poor prognostic factors. After treated by 5-Aza-CdR and TSA, we found that MUC2 mRNA induced significantly in 7721, Huh7 and HepG2 cells.ConclusionThe results suggested that MUC2 mRNA silenced by promoter hypermethylation is associated with high levels HBV in HCC.
Highlights
To evaluate the promoter methylation status of MUC2 gene and mRNA expression in patients with hepatocellular carcinoma
We found that MUC2 mRNA expression lower in HCC tissues (Mean -ΔCt = −4.70; 95% CI, -5.88 – -3.53) than that in Non-HCC tissues (Mean -ΔCt = −2.98; 95% CI, -3.99 – -1.97)
The MUC2 mRNA in HCC was lower than that in the matched non-tumor liver tissues (p < 0.0001). (B) There was a decreased tendency for MUC2 expression from Non-HCC tissues to HCC. (C) Expression of MUC2 was elevated (−ΔΔCt > =0) in only 23 of the 74 HCC patients but decreased (−ΔΔCt < 0) in 51 of the patients
Summary
To evaluate the promoter methylation status of MUC2 gene and mRNA expression in patients with hepatocellular carcinoma. MUC2 is the major secreted mucin in the large and small intestine with an O-linked carbohydrate. MUC2 presents in normal gastrointestinal secretion products and epithelia, and in some tumors [3]. The presence of MUC2 protein was not demonstrable by immunohistochemical staining cholangiocarcinoma [10,11]. MUC2 expression were observed in 42.0% of 193 extrahepatic bile duct carcinomas [12]. The conventional intrahepatic cholangiocarcinoma (ICC) frequently expressed MUC5AC, but no MUC2, in carcinoma cells. The expression of MUC2 seems to be a specific feature of mucinous ICC and Intraductal papillary neoplasia of the liver [13]. The results regarding correlations of MUC2 expression in cancer are contradictory [16]
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