DNA Damage Sensor γ-H2AX Is Increased in Preneoplastic Lesions of Hepatocellular Carcinoma

Background. Phosphorylated histone H2AX (γ-H2AX) is a potential regulator of DNA repair and is a useful tool for detecting DNA damage. To evaluate the clinical usefulness of γ-H2AX in hepatocellular carcinoma (HCC), we measured the level of γ-H2AX in HCC, dysplastic nodule, and nontumorous liver dis...

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Main Authors: Yasunobu Matsuda, Toshifumi Wakai, Masayuki Kubota, Mami Osawa, Masaaki Takamura, Satoshi Yamagiwa, Yutaka Aoyagi, Ayumi Sanpei, Shun Fujimaki
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1155/2013/597095
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author Yasunobu Matsuda
Toshifumi Wakai
Masayuki Kubota
Mami Osawa
Masaaki Takamura
Satoshi Yamagiwa
Yutaka Aoyagi
Ayumi Sanpei
Shun Fujimaki
author_facet Yasunobu Matsuda
Toshifumi Wakai
Masayuki Kubota
Mami Osawa
Masaaki Takamura
Satoshi Yamagiwa
Yutaka Aoyagi
Ayumi Sanpei
Shun Fujimaki
author_sort Yasunobu Matsuda
collection DOAJ
description Background. Phosphorylated histone H2AX (γ-H2AX) is a potential regulator of DNA repair and is a useful tool for detecting DNA damage. To evaluate the clinical usefulness of γ-H2AX in hepatocellular carcinoma (HCC), we measured the level of γ-H2AX in HCC, dysplastic nodule, and nontumorous liver diseases. Methods. The level of γ-H2AX was measured by immunohistochemistry in fifty-eight HCC, 18 chronic hepatitis, 22 liver cirrhosis, and 19 dysplastic nodules. Appropriate cases were also examined by fluorescence analysis and western blotting. Results. All cases with chronic liver disease showed increased levels of γ-H2AX expression. In 40 (69.9%) of 58 cases with HCC, the labeling index (LI) of γ-H2AX was above 50% and was inversely correlated with the histological grade. Mean γ-H2AX LI was the highest in dysplastic nodule (74.1±22.1%), which was significantly higher than HCC (P<0.005). Moreover, γ-H2AX was significantly increased in nontumorous tissues of HCC as compared with liver cirrhosis without HCC (62.5±24.7%, from 5.1 to 96.0%, P<0.005). Conclusions. γ-H2AX was increased in the preneoplastic lesions of HCC and might be a useful biomarker for predicting the risk of HCC.
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spelling doaj-art-a5ad762b360e478b8d732ec1adb7a2d92025-02-03T06:13:10ZengWileyThe Scientific World Journal1537-744X2013-01-01201310.1155/2013/597095597095DNA Damage Sensor γ-H2AX Is Increased in Preneoplastic Lesions of Hepatocellular CarcinomaYasunobu Matsuda0Toshifumi Wakai1Masayuki Kubota2Mami Osawa3Masaaki Takamura4Satoshi Yamagiwa5Yutaka Aoyagi6Ayumi Sanpei7Shun Fujimaki8Department of Medical Technology, Niigata University Graduate School of Health Sciences, 2-746 Asahimachi-dori, Niigata 951-8518, JapanDivision of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 2-746 Asahimachi-dori, Niigata 951-8518, JapanDivision of Pediatric Surgery, Niigata University Graduate School of Medical and Dental Sciences, 2-746 Asahimachi-dori, Niigata 951-8518, JapanDivision of Pediatric Surgery, Niigata University Graduate School of Medical and Dental Sciences, 2-746 Asahimachi-dori, Niigata 951-8518, JapanDivision of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 2-746 Asahimachi-dori, Niigata 951-8518, JapanDivision of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 2-746 Asahimachi-dori, Niigata 951-8518, JapanDivision of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 2-746 Asahimachi-dori, Niigata 951-8518, JapanDepartment of Medical Technology, Niigata University Graduate School of Health Sciences, 2-746 Asahimachi-dori, Niigata 951-8518, JapanDepartment of Medical Technology, Niigata University Graduate School of Health Sciences, 2-746 Asahimachi-dori, Niigata 951-8518, JapanBackground. Phosphorylated histone H2AX (γ-H2AX) is a potential regulator of DNA repair and is a useful tool for detecting DNA damage. To evaluate the clinical usefulness of γ-H2AX in hepatocellular carcinoma (HCC), we measured the level of γ-H2AX in HCC, dysplastic nodule, and nontumorous liver diseases. Methods. The level of γ-H2AX was measured by immunohistochemistry in fifty-eight HCC, 18 chronic hepatitis, 22 liver cirrhosis, and 19 dysplastic nodules. Appropriate cases were also examined by fluorescence analysis and western blotting. Results. All cases with chronic liver disease showed increased levels of γ-H2AX expression. In 40 (69.9%) of 58 cases with HCC, the labeling index (LI) of γ-H2AX was above 50% and was inversely correlated with the histological grade. Mean γ-H2AX LI was the highest in dysplastic nodule (74.1±22.1%), which was significantly higher than HCC (P<0.005). Moreover, γ-H2AX was significantly increased in nontumorous tissues of HCC as compared with liver cirrhosis without HCC (62.5±24.7%, from 5.1 to 96.0%, P<0.005). Conclusions. γ-H2AX was increased in the preneoplastic lesions of HCC and might be a useful biomarker for predicting the risk of HCC.http://dx.doi.org/10.1155/2013/597095
spellingShingle Yasunobu Matsuda
Toshifumi Wakai
Masayuki Kubota
Mami Osawa
Masaaki Takamura
Satoshi Yamagiwa
Yutaka Aoyagi
Ayumi Sanpei
Shun Fujimaki
DNA Damage Sensor γ-H2AX Is Increased in Preneoplastic Lesions of Hepatocellular Carcinoma
The Scientific World Journal
title DNA Damage Sensor γ-H2AX Is Increased in Preneoplastic Lesions of Hepatocellular Carcinoma
title_full DNA Damage Sensor γ-H2AX Is Increased in Preneoplastic Lesions of Hepatocellular Carcinoma
title_fullStr DNA Damage Sensor γ-H2AX Is Increased in Preneoplastic Lesions of Hepatocellular Carcinoma
title_full_unstemmed DNA Damage Sensor γ-H2AX Is Increased in Preneoplastic Lesions of Hepatocellular Carcinoma
title_short DNA Damage Sensor γ-H2AX Is Increased in Preneoplastic Lesions of Hepatocellular Carcinoma
title_sort dna damage sensor γ h2ax is increased in preneoplastic lesions of hepatocellular carcinoma
url http://dx.doi.org/10.1155/2013/597095
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