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Series GSE103205 Query DataSets for GSE103205
Status Public on Aug 29, 2017
Title Gene expression profiling of hepatocarcinogenesis in a mouse model of chronic hepatitis B
Organism Mus musculus
Experiment type Expression profiling by array
Summary BACKGROUND: Hepatocellular carcinoma (HCC) is a common complication of chronic viral hepatitis. In support of this notion, we have reported that hepatitis B surface antigen (HBsAg)-specific CD8+ T lymphocytes critically contribute to inducing chronic liver cell injury that exerts high carcinogenic potential in a hepatitis B virus (HBV) Tg mouse model. The dynamics of the molecular signatures responsible for hepatocellular carcinogenesis are not fully understood. The current study was designed to determine the serial changes in gene expression profiles in a model of chronic immune-mediated hepatitis.

METHODS: Three-month-old HBV Tg mice were immunologically reconstituted with bone marrow cells and splenocytes from syngeneic nonTg donors. Liver tissues were obtained every three months until 18 months at which time all mice developed multiple liver tumors. Nitrative DNA lesions and hepatocyte turnover were assessed immunohistochemically. Gene expression profiles were generated by extracting total RNA from the tissues and analyzing by microarray.

RESULTS: The nitrative DNA lesions and the regenerative proliferation of hepatocytes were increased during the progression of chronic liver disease. In a gene expression profile analysis of liver samples, the chemokine- and T cell receptor (TCR)-mediated pathways were enhanced during chronic hepatitis, and the EGF- and VEGF-mediated pathways were induced in HCC. Among these molecules, the protein levels of STAT3 were greatly enhanced in all hepatocyte nuclei and further elevated in the cytoplasm in HCC tissue samples at 18 months, and the levels of phosphorylated TP53 (p-p53-Ser 6 and -Ser 15) were increased in liver tissues.

CONCLUSIONS: HBV-specific immune responses caused unique molecular signatures in the liver tissues of chronic hepatitis and triggered subsequent carcinogenic gene expression profiles in a mouse model. The results suggest a plausible molecular basis responsible for HBV-induced immune pathogenesis of HCC.
 
Overall design The comprehensive gene expression profiles in the mouse livers, five immunologically reconstituted HBV Tg mice were sacrificed on day 7 and every three months until 18 months. The comparison combinations used in this analysis were the average values of log-ratios against Tg mix of Tg7d, Tg1M, Tg3M, Tg6M, Tg9M, Tg12M, Tg15M, Tg18M, and tumor (Tg18M) and the log ratios of Tg18M/Tg mix and tumor (Tg18M)/ Tg mix.
 
Contributor(s) Nosaka T, Naito T, Hiramatsu K, Ohtani M, Nemoto T, Marusawa H, Ma N, Hiraku Y, Kawanishi S, Yamashita T, Kaneko S, Nakamoto Y
Citation(s) 28968425
Submission date Aug 28, 2017
Last update date Jul 25, 2021
Contact name Takuto Nosaka
E-mail(s) nosat@u-fukui.ac.jp
Phone +81-776-61-8351
Organization name University of Fukui
Department Second Department of Internal Medicine
Street address 23-3 Matsuoka, Eiheiji-cho
City Yoshida-gun
State/province Fukui
ZIP/Postal code 910-1193
Country Japan
 
Platforms (1)
GPL2872 Agilent-012694 Whole Mouse Genome G4122A (Feature Number version)
Samples (45)
GSM2757351 Liver_HBV Tg mouse_7d_rep1
GSM2757352 Liver_HBV Tg mouse_7d_rep2
GSM2757353 Liver_HBV Tg mouse_7d_rep3
Relations
BioProject PRJNA400489

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE103205_RAW.tar 527.5 Mb (http)(custom) TAR (of TXT)
GSE103205_normalized_data_with_annotation.txt.gz 21.0 Mb (ftp)(http) TXT
Processed data included within Sample table
Processed data are available on Series record

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