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Up-regulated aldo-keto reductase family 1 member B10 in chronic hepatitis C: association with serum alpha-fetoprotein and hepatocellular carcinoma
BACKGROUND: Elevated serum alpha-fetoprotein (AFP) is not only a diagnostic marker for hepatocellular carcinoma (HCC), but is also a risk factor for HCC in chronic hepatitis C patients who do not have HCC. AIM: The aim was to analyse the hepatic gene expression signature in chronic hepatitis C patie...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466415/ https://www.ncbi.nlm.nih.gov/pubmed/22681639 http://dx.doi.org/10.1111/j.1478-3231.2012.02827.x |
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author | Sato, Shunsuke Genda, Takuya Hirano, Katsuharu Tsuzura, Hironori Narita, Yutaka Kanemitsu, Yoshio Kikuchi, Tetsu Iijima, Katsuyori Wada, Ryo Ichida, Takafumi |
author_facet | Sato, Shunsuke Genda, Takuya Hirano, Katsuharu Tsuzura, Hironori Narita, Yutaka Kanemitsu, Yoshio Kikuchi, Tetsu Iijima, Katsuyori Wada, Ryo Ichida, Takafumi |
author_sort | Sato, Shunsuke |
collection | PubMed |
description | BACKGROUND: Elevated serum alpha-fetoprotein (AFP) is not only a diagnostic marker for hepatocellular carcinoma (HCC), but is also a risk factor for HCC in chronic hepatitis C patients who do not have HCC. AIM: The aim was to analyse the hepatic gene expression signature in chronic hepatitis C patients with elevated AFP, who were at high risk for HCC. METHODS: Liver tissue samples from 48 chronic hepatitis C patients were stratified by their serum AFP levels and analysed for gene expression profiles. The association between aldo-keto reductase family 1 member B10 (AKR1B10) expression and serum AFP was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analyses. A matched case-control study was performed to evaluate the risk of AKR1B10 expression for HCC development. RESULTS: Distinct hepatic gene expression patterns were demonstrated in patients with elevated AFP (≥10 ng/mL) and normal AFP (<10 ng/mL). Of the 627 differently expressed genes, the most abundantly expressed gene in patients with elevated AFP was AKR1B10 (fold change, 26.2; P < 0.001), which was originally isolated as an overexpressed gene in human HCC. The qRT-PCR and immunohistochemical studies confirmed a proportional correlation between AKR1B10 expression and serum AFP. A matched case-control study identified that AKR1B10 up-regulation (>6%) was an independent risk factor for HCC development (hazard ratio, 21.4; P = 0.001). CONCLUSION: AKR1B10 was up-regulated in association with serum AFP, and was an independent risk factor for HCC in chronic hepatitis C patients, suggesting its possible involvement at a very early stage of hepatocarcinogenesis. |
format | Online Article Text |
id | pubmed-3466415 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-34664152012-10-11 Up-regulated aldo-keto reductase family 1 member B10 in chronic hepatitis C: association with serum alpha-fetoprotein and hepatocellular carcinoma Sato, Shunsuke Genda, Takuya Hirano, Katsuharu Tsuzura, Hironori Narita, Yutaka Kanemitsu, Yoshio Kikuchi, Tetsu Iijima, Katsuyori Wada, Ryo Ichida, Takafumi Liver Int Clinical Studies BACKGROUND: Elevated serum alpha-fetoprotein (AFP) is not only a diagnostic marker for hepatocellular carcinoma (HCC), but is also a risk factor for HCC in chronic hepatitis C patients who do not have HCC. AIM: The aim was to analyse the hepatic gene expression signature in chronic hepatitis C patients with elevated AFP, who were at high risk for HCC. METHODS: Liver tissue samples from 48 chronic hepatitis C patients were stratified by their serum AFP levels and analysed for gene expression profiles. The association between aldo-keto reductase family 1 member B10 (AKR1B10) expression and serum AFP was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analyses. A matched case-control study was performed to evaluate the risk of AKR1B10 expression for HCC development. RESULTS: Distinct hepatic gene expression patterns were demonstrated in patients with elevated AFP (≥10 ng/mL) and normal AFP (<10 ng/mL). Of the 627 differently expressed genes, the most abundantly expressed gene in patients with elevated AFP was AKR1B10 (fold change, 26.2; P < 0.001), which was originally isolated as an overexpressed gene in human HCC. The qRT-PCR and immunohistochemical studies confirmed a proportional correlation between AKR1B10 expression and serum AFP. A matched case-control study identified that AKR1B10 up-regulation (>6%) was an independent risk factor for HCC development (hazard ratio, 21.4; P = 0.001). CONCLUSION: AKR1B10 was up-regulated in association with serum AFP, and was an independent risk factor for HCC in chronic hepatitis C patients, suggesting its possible involvement at a very early stage of hepatocarcinogenesis. Blackwell Publishing Ltd 2012-10 2012-06-11 /pmc/articles/PMC3466415/ /pubmed/22681639 http://dx.doi.org/10.1111/j.1478-3231.2012.02827.x Text en © 2012 John Wiley & Sons A/S http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
spellingShingle | Clinical Studies Sato, Shunsuke Genda, Takuya Hirano, Katsuharu Tsuzura, Hironori Narita, Yutaka Kanemitsu, Yoshio Kikuchi, Tetsu Iijima, Katsuyori Wada, Ryo Ichida, Takafumi Up-regulated aldo-keto reductase family 1 member B10 in chronic hepatitis C: association with serum alpha-fetoprotein and hepatocellular carcinoma |
title | Up-regulated aldo-keto reductase family 1 member B10 in chronic hepatitis C: association with serum alpha-fetoprotein and hepatocellular carcinoma |
title_full | Up-regulated aldo-keto reductase family 1 member B10 in chronic hepatitis C: association with serum alpha-fetoprotein and hepatocellular carcinoma |
title_fullStr | Up-regulated aldo-keto reductase family 1 member B10 in chronic hepatitis C: association with serum alpha-fetoprotein and hepatocellular carcinoma |
title_full_unstemmed | Up-regulated aldo-keto reductase family 1 member B10 in chronic hepatitis C: association with serum alpha-fetoprotein and hepatocellular carcinoma |
title_short | Up-regulated aldo-keto reductase family 1 member B10 in chronic hepatitis C: association with serum alpha-fetoprotein and hepatocellular carcinoma |
title_sort | up-regulated aldo-keto reductase family 1 member b10 in chronic hepatitis c: association with serum alpha-fetoprotein and hepatocellular carcinoma |
topic | Clinical Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466415/ https://www.ncbi.nlm.nih.gov/pubmed/22681639 http://dx.doi.org/10.1111/j.1478-3231.2012.02827.x |
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