Evidence map›Paper›PMID 37732511›Full record

ArticleCancer medicine2023

Immunohistochemical expression of NRF2 is correlated with the magnitude of inflammation and fibrosis in chronic liver disease.

Keii To, Kosuke Okada, Takahisa Watahiki, Hideo Suzuki, Kiichiro Tsuchiya, Katsutoshi Tokushige, Masakazu Yamamoto, Shun-Ichi Ariizumi, Junichi Shoda

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

Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

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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

9 authors at 2 institutions in 1 country.

Keii ToDepartment of Gastroenterology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.ORCID 0009-0000-9116-2854
Kosuke OkadaDepartment of Gastroenterology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.
Takahisa WatahikiDepartment of Gastroenterology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.
Hideo SuzukiDepartment of Gastroenterology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.
Kiichiro TsuchiyaDepartment of Gastroenterology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.
Katsutoshi TokushigeInstitute of Gastroenterology and Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Masakazu YamamotoDepartment of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
Shun-Ichi AriizumiDepartment of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
Junichi ShodaDivision of Medical Sciences, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.
University of Tsukuba · JPTokyo Women's Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe nuclear factor E2-related factor 2-Kelch-like Ech-associated protein (NRF2-KEAP1) pathway is a major cellular defense mechanism against oxidative stress. However, the role of NRF2-KEAP1 signaling in the development of chronic liver disease remains unclear.

methodsClinical liver specimens from 50 hepatocellular carcinoma (HCC) developed from non-alcoholic steatohepatitis (NASH), 49 HCCs developed from chronic viral hepatitis C (CHc), and 48 liver metastases of colorectal cancer (CRC) from both tumorous and non-tumorous areas were collected during hepatic resection surgery. They were evaluated by immunohistochemical analyses of hematoxylin-eosin, Masson's trichrome, NRF2, and KEAP1, and compared with clinicopathological information.

resultsHepatic inflammation and fibrosis were more severe in the low-intensity NRF2 group than in the high-intensity NRF2 group both between CRC and NASH (Low vs. High: inflammation; p = 0.003, fibrosis; p = 0.014), and between CRC and CHc (Low vs. High: inflammation; p = 0.031, fibrosis; p = 0.011), which could indicate that NRF2 expression in cytosol of hepatocytes was inversely correlated with liver inflammation and fibrosis in non-tumorous areas. The dense staining of NRF2 in the nuclei of non-tumor hepatocytes positively correlated with liver inflammation (CRC and NASH; R = 0.451, p < 0.001, CRC and CHc; R = 0.502, p < 0.001) and fibrosis (CRC and NASH; R = 0.566, p < 0.001, CRC and CHc; R = 0.548, p < 0.001) in both NASH and CHc, and was inversely correlated with hepatic spare ability features such as platelet count (R = -0.253, p = 0.002) and prothrombin time (R = -0.206, p = 0.012). However, KEAP1 expression was not correlated with NRF2 expression levels and nuclear staining intensity.

conclusionsNuclear translocation of NRF2 was correlated with the magnitude of liver inflammation and fibrosis in chronic liver disease. These results suggest that NRF2 plays a protective role in the development of chronic liver diseases such as NASH and CHc.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsNon-alcoholic Fatty Liver DiseaseFibrosisHumansInflammationKelch-Like ECH-Associated Protein 1LiverLiver CirrhosisNF-E2-Related Factor 2Kelch-Like ECH-Associated Protein 1NF-E2-Related Factor 2chronic liver diseasehepatocellular carcinomaKEAP1NASHNRF2

Identifiers

PMID37732511
PMCPMC10587934
OpenAlexW4386910911

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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.