Evidence map›Paper›PMID 28968425›Full record

ArticlePloS one2017

Gene expression profiling of hepatocarcinogenesis in a mouse model of chronic hepatitis B.

Takuto Nosaka, Tatsushi Naito, Katsushi Hiramatsu, Masahiro Ohtani, Tomoyuki Nemoto, Hiroyuki Marusawa, Ning Ma, Yusuke Hiraku, Shosuke Kawanishi, Taro Yamashita and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
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  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 1 country.

Takuto NosakaSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, Japan.ORCID http://orcid.org/0000-0002-1929-7305
Tatsushi NaitoSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, Japan.
Katsushi HiramatsuSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, Japan.
Masahiro OhtaniSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, Japan.
Tomoyuki NemotoSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, Japan.
Hiroyuki MarusawaDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Sakyo-Ku, Kyoto, Japan.
Ning MaFaculty of Nursing Science, Suzuka University of Medical Science, Suzuka, Mie, Japan.
Yusuke HirakuDepartment of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Shosuke KawanishiFaculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, Japan.
Taro YamashitaDepartment of Gastroenterology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
Shuichi KanekoDepartment of Gastroenterology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
Yasunari NakamotoSecond Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, Japan.ORCID http://orcid.org/0000-0002-3160-3555
University of Fukui · JPKanazawa University · JPSuzuka University of Medical Science · JPKyoto University · JPMie University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHepatocellular 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) transgenic 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.

methodsThree-month-old HBV transgenic mice were immunologically reconstituted with bone marrow cells and splenocytes from syngeneic nontransgenic 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.

resultsThe 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.

conclusionsHBV-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.

Indexed as

Disease Models, AnimalGene Expression ProfilingAnimalsCarcinogenesisCarcinoma, HepatocellularDNA, ComplementaryGenes, p53Hepatitis B, ChronicLiverLiver NeoplasmsMaleMiceMice, TransgenicOligonucleotide Array Sequence AnalysisSTAT3 Transcription FactorDNA, ComplementaryStat3 protein, mouseSTAT3 Transcription Factor

Identifiers

PMID28968425
PMCPMC5624708
OpenAlexW2763802939

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.