[Correlation between epigenetic alterations in the insulin growth factor-II gene and hepatocellular carcinoma].

Objective To investigate whether epigenetic alterations in the iusulin-like growth factorⅡ (IGF-1Ⅱ) gene that cause differential transcription or expression are correlated with onset and severity of hepatocellular carcinoma (HCC).Methods Patient-matched specimens of HCC,paracancerous,and non-cancerous tissues were collected from 40 primary liver cancer patients.Epigenetic alterations in the promoter (P3) sequence of the IGF-Ⅱ gene were analyzed by methylation-specific PCR (MSP) and IGF-Ⅱ transcription was measured by RT-PCR.IGF-Ⅱ protein expression and clinicopathological features were nssessed by immunohistochemistry and microscopic observation.Results The rate of IGF-Ⅱ P3 methylation was significantly lower in HCC tissues (0％) than in paracancerous tissues (vs.47.5％; X2=24.918,P＜0.001) and non-cancerous tissues (vs.100％;x2=80.000,P＜0.001).IGF-Ⅱ mRNA expression was significantly higher in HCC tissues (100％) than in paracancerous tissues (vs.52.5％;x2=24.918,P＜0.001) and non-cancerous tissues (vs.0％;x2 =80.000,P＜0.001).IGF-Ⅱ protein expression was significantly higher in HCC tissues (82.5％) than in paracancerous tissues (vs.45.0％;X2=12.170,P＜0.001) and non-cancerous tissues (vs.0％;X2=56.170,P＜0.001).IGF-Ⅱ overexpression in HCC was significantly associated with degree of differentiation,extent of infiltrated serosa,size of tumor,and HBV-positive infection status.Conclusion Epigenetic alterations in the IGF-Ⅱ gene regulate its transcription and expression and are closely associated with HCC development and progression. Key words: Carcinoma,hepatocellular; Insuline-like growth factor-Ⅱ; Gene amplifercation;  Methylation; Transcription