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An integrated analysis of SOCS 1 down‐regulation in HBV infection‐related hepatocellular carcinoma
Author(s) -
Zhang X.,
Wang J.,
Cheng J.,
Ding S.,
Li M.,
Sun S.,
Zhang L.,
Liu S.,
Chen X.,
Zhuang H.,
Lu F.
Publication year - 2014
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12137
Subject(s) - hepatocellular carcinoma , methylation , suppressor of cytokine signaling 1 , cancer research , dna methylation , epigenetics , biology , hepatitis b virus , cirrhosis , gene , microbiology and biotechnology , medicine , gene expression , immunology , virus , suppressor , genetics
Summary Persistent inflammation together with genetic/epigenetic aberrations is strongly associated with chronic H epatitis B virus ( HBV ) infection‐related hepatocarcinogenesis. Here, we investigated the alterations of the suppressor of cytokine signalling ( SOCS ) family genes in HBV ‐related hepatocellular carcinoma ( HCC ). A total of 116 patients with HCC were enrolled in this study. The methylation statuses of SOCS 1‐7 and CISH genes were quantitatively measured and clinicopathological significance of SOCS 1 methylation was statistically analysed. The gene copy number variation was assayed by a CGH . Luciferase reporter assay and Western blot were used to detect the involvement of SOCS 1 in p53 signalling. We found high frequencies of SOCS1 gene hypermethylation in both tumour (56.03%) and adjacent nontumour tissues (54.31%), but tumour tissues exhibited increased methylation intensity (24.01% vs 13.11%, P < 0.0001), particularly in patients with larger tumour size or cirrhosis background ( P < 0.0001). In addition, the frequency and intensity of SOCS 1 hypermethylation in tumour tissues were both significantly higher than those in nontumour tissues in male gender patients and in patients ≥45 years old ( P = 0.0214 and P < 0.0001, P = 0.0232 and P < 0.0001, respectively). SOCS 1 gene deletion was found in 8 of 25 a CGH assayed tumour specimens, which was associated with lower SOCS 1 m RNA expression ( P = 0.0448). Furthermore, ectopic SOCS 1 overexpression could activate the p53 signalling pathway in HCC cell lines. Hypermethylation of SOCS 2‐7 and CISH genes was seldom found in HCC . Our results suggested that the gene loss and epigenetic silencing of SOCS 1 were strongly associated with HBV ‐related HCC .