Estrogen receptor levels and lipid peroxidation in hepatocellular carcinoma with hepatitis C virus infection
Estrogen receptor levels and lipid peroxidation in hepatocellular carcinoma with hepatitis C virus infection
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DOI：
10.1034/j.1600-0676.2001.210507.x
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发表时间：
2001-10-01
期刊：
影响因子：
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通讯作者：
Ito, S
中科院分区：
文献类型：
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作者：
Shimizu, I;Inoue, H;Ito, S
目的/背景。我们的初步研究表明，雌二醇抑制肝癌和肝纤维化的动物模型。肝脏雌激素受体（ER）在肝脏中取代雌二醇的作用。本研究旨在评估绝经和肝脏ER水平对肝硬化伴肝细胞癌（HCC）发展的可能影响。方法.将1199例连续的丙型肝炎病毒（HCV）相关肝硬化HCC患者分为两组，绝经年龄为49岁。肝组织是在手术切除HCC和转移性肝肿瘤时获得的。结果HCC受试者中年龄小于或等于49岁的女性比例（15.0%）显著低于年龄> 49岁的女性比例（29.8%）。单因素分析显示，HCV相关的肝硬化患者发展为肝癌更可能有低水平的ER和铜锌超氧化物歧化酶（CuZn-SOD）蛋白和高水平的脂质过氧化产物，丙二醛（MDA）的肝脏。Logistic回归确定年龄大于49岁（比值比[OR]：7.9，95%，置信区间[CII：2.8-21.3），男性（OR：3.5，95% CI：1.3-10.2），ER水平降低（OR：16.8，95% CI：7.3-34.6），MDA增加（OR：8.3，95%CI：2.8-24.0）作为与HCV感染合并肝硬化患者发生HCC独立相关的变量。ER水平与CuZn-SOD水平呈显著正相关（r=0.583），与MDA水平呈负相关（r=-0.553）。该研究还表明，绝经前女性患者肝脏中的ER水平显著高于男性患者肝脏。结论.这些研究结果表明，增加脂质过氧化和受损的SOD功能在肝脏中可能与肝硬化和HCC的HCV感染患者的肝脏ER水平下降，和HCV相关的绝经前的女性可能有能力保护发展肝癌通过肝脏ER。关键电话：
Aims/Background. Our preliminary studies showed that estradiol suppresses hepatic carcinogenesis and fibrogenesis in animal models. Hepatic estrogen receptors (ERs) medicate estradiol action in the liver. This study was performed to assess possible implications of menopause and hepatic ER levels for the development of cirrhosis with hepatocellular carcinoma (HCC). Methods. One thousand, one hundred and ninety-nine consecutive HCC patients with hepatitis C virus (HCV)-related cirrhosis were divided into two groups, based on a menopausal age of 49 years. Liver tissues were obtained during surgical resection of HCC and metastatic liver tumor. Results. The proportion of females among the HCC subjects less than or equal to 49 years of age was significantly lower (15.0%) than was the proportion of females among subjects > 49 years of age (29.8%). Univariate analysis showed that HCV-related cirrhotic patients who developed HCC were more likely to have low hepatic levels of ER and copper-zinc superoxide dismutase (CuZn-SOD) protein and a high hepatic level of a lipid peroxidation product, malondialdehyde (MDA). Logistic regression identified age greater than 49 years (odds ratio [OR]: 7.9, 95%, confidence interval [CII: 2.8-21.3), male sex (OR: 3.5, 95% CI: 1.3-10.2), a decreased ER level (OR: 16.8, 95% CI: 7.3-34.6), and an increased MDA (OR: 8.3, 95% CI: 2.8-24.0) as the variables independently associated with the development of HCC in HCV-infected patients with cirrhosis. ER level was significantly correlated with CuZn-SOD level (r=0.583) and was inversely proportional to MDA level (r=-0.553). The study also showed that ER levels in the cirrhotic livers from premenopausal females were significantly higher than in male cirrhotic livers. Conclusions. These findings suggest that increased lipid peroxidation and impaired SOD function in the liver may be associated with decreased hepatic ER levels in HCV-infected patients with cirrhosis and HCC, and that HCV-related cirrhotic women before menopause might have the ability to protect against developing HCC via hepatic ER. Key Tel: