肝细胞癌cpg岛甲基化谱和临床病理关系-methylation profile of cpg island in hepatocellular carcinoma and its clinicopathological relationship.docxVIP

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肝细胞癌cpg岛甲基化谱和临床病理关系-methylation profile of cpg island in hepatocellular carcinoma and its clinicopathological relationship.docx

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肝细胞癌cpg岛甲基化谱和临床病理关系-methylation profile of cpg island in hepatocellular carcinoma and its clinicopathological relationship

汕头大汕头大学硕士学位论文IVIVtissues by methylation-specific PCR and determined a hypermethylation profile in HCC. In this study, CIMP status was classified as CIMP+ samples (with 5 or more methylated genes) and CIMP- (samples with 4 or fewer methylated genes).We found that the frequency of promoter methylation of nine genes in 50 HCC varied from 10% in P53 to 94% in c-Myc. Methylation status of P14, P15, P16, ER, RASSF1A, WT1, and c-Myc was significantly correlated with HCC and non-tumor tissues (p 0.05). Hypermethylation of one or more genes was found in 96% of HCC. CIMP was more frequent inHCC than in non-tumor tissues (70% and 12%, p 0.001)，no CIMP+ was present in normalliver tissues. There is a significant association between CIMP and methylation of P14, P15, P16, ER, RASSF1A and WT1 (p 0.05) and serum alpha fetoprotein (AFP) level (p = 0.001). CIMP+ was more frequent in HCC with AFP ≥ 30 ug/l than those with AFP 30 ug/l (p = 0.005). Also, the promoter hypermethylation of P15 and P16 was associated with elevated serum AFP levels in 35 HCC samples with CIMP+ (p 0.05). There was no statistically significant association between CIMP status and age, gender, tumor size, smoking history, drinking alcohol, HBV, HCV, cirrhosis, node number, and metastasis.The results suggest that the simultaneous hypermethylation of multiple tumor-related genes may be important for tumorigenesis. CIMP is also present in liver cancers and could be a critical event for malignant transformation from liver cirrhosis to HCC. Functional inactivation of P15 and P16 mediated by promoter methylation may be required for aberrant expression of AFP during hepatocarcinogenesis. Positive correlation of CIMP and AFP levels suggests that CIMP can serve as a molecular marker of poor prognosis of in HCC.Keyword HCC; methylation; CpG island methylator phenotype; AFP PAGE PAGE VI缩略词表缩写英文全称中文全称5-Aza-dC5-aza-2-deoxycytidine5-氮杂胞苷5-mC5-methyl cytosine5 一甲基胞嘧啶AFPalpha-fetoprotein甲胎蛋白bpbase pair碱基对CIMPCpG isla