eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2015-04-28 6 2 177 187 10.13005/bpj/401 2673 article Zhizhen Dong 1 Min Yao 2 Li Wang 3 Xing Gu 4 Yun Shi 4 Hua Huang 5 Department of Diagnostics, Affiliated Hospital of Nantong University, Jiangsu Province, 226001, China. Department of Immunology, Medical School of Nantong University, Jiangsu Province, 226001, China. Department of Informatics, Medical School of Nantong University, Jiangsu Province, 226001, China. Department of Oncology, Affiliated Hospital of Nantong University, Jiangsu Province, 226001, China. Department of Pathology, Affiliated Hospital of Nantong University, Jiangsu Province, 226001, China. Abnormal expression of liver insulin-like growth factor-II (IGF-II) regulating by the methylation of its gene promoter (P1~4) CpG islands through epigenetic silencing of fetal P2, P3, and P4, or adult P1 is associated with progression of HBV-related hepatocellular carcinoma (HCC). The aims of the present study were to investigate the alteration of methylational status in P3 region CpG islands, and analyze IGF-II expression and clinicopathological features in HBV-related HCC. The methylational status of P3 region CpG islands was observed in the matched parts of HCC tissues by methylation-specific PCR. Hepatic IGF-II expression was analyzed by immunohistochemistry. IGF-II mRNA was amplified by RT-PCR, and confirmed by sequencing. Serum IGF-II levels were quantitatively detected by ELISA assay. The frequencies of IGF-II mRNA positive fragment, IGF-II positive, and the P3 hypomethylated CpG islands were 100%, 87.5%, and 100% in HCC-, 53.3%, 47.5%, and 52.5% in paracancerous-, and none in noncancerous-tissues, respectively. Significant IGF-II expression in HCC tissues was related to differentiation degree (moderate or poor), tumor invasion, and positive-HBV DNA (P<0.05). An inverse correlation was found between P3 methylational degree and IGF-II expression. The levels of hepatic IGF-II and serum IGF-II expression were significantly elevated (P<0.001) in the HCC group more than any of the other groups. Abnormality of hepatic IGF-II expression is associated with hypomethylational status of its fetal promoter CpG sites, and circulating IGF-II abnormality is a useful biomarker for HCC diagnosis. https://biomedpharmajournal.org/vol6no2/epigenetic-alterations-of-hepatic-igf-ii-gene-promoter-and-igf-ii-abnormal-expression-in-hbv-related-hepatocellular-carcinoma/ Hepatocellular carcinoma Insulin-like growth factor-II Promoter Methylation-specific PCR Diagnosis Biomarker