Expression of proteins upregulated in hepatocellular carcinoma in patients with alcoholic hepatitis (AH) compared to non-alcoholic steatohepatitis (NASH): An immunohistochemical analysis of candidate proteins.

Expression of proteins upregulated in hepatocellular carcinoma in patients with alcoholic hepatitis (AH) compared to non-alcoholic steatohepatitis (NASH): An immunohistochemical analysis of candidate proteins.
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DOI:
10.1016/j.yexmp.2018.02.001
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发表时间:
2018-04
影响因子:
3.6
通讯作者:
French SW
French SW
中科院分区:
医学3区
文献类型:
--
作者:
Lu JG;Nguyen L;Samadzadeh S;Masouminia M;Mendoza A;Sweeney O;Tillman B;Afifyan N;Morgan T;French BA;French SW

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非酒精性脂肪性肝炎(NASH)和酒精性肝炎(AH)均可导致肝硬化和肝细胞癌。然而,AH进展为肝硬化和肿瘤发生的速率大于NASH。我们问是否有差异,这两种条件下的蛋白质的表达水平参与肝细胞癌的发病机制。在2017年美国肝病研究协会(AASLD)肝脏会议上,检测的蛋白质在肝细胞癌中过表达:KLF 4,SCL 19 A1,FANCG,HRH-1,DNMT 1,DNMT 3B,TNFR 2,DUSP 4,EGFR,整合素α6,HDACII,PDE 3A,BCL-XL和MTCO 2。使用荧光抗体免疫组织化学染色,然后通过形态学定量荧光强度,在NASH和AH患者的肝活检切片中测量这些蛋白质的表达。在AH患者中,与正常患者相比,除HRH-1外的所有测试蛋白质的水平均升高。与正常对照组相比,NASH患者的KLF 4、SCL 19 A1、FANCG、HDAC II、BCL-XL水平升高,而HRH-1、DNMT 1和PDE 3A水平降低。除BCL-XL外,研究的所有蛋白质的相对表达在AH中均显著高于NASH。总之,与NASH和正常肝脏相比,参与肝细胞癌发展的蛋白质在AH中的表达更高,这与AH患者中肿瘤发生率高于NASH患者相对应。
Both non-alcoholic steatohepatitis (NASH) and alcoholic hepatitis (AH) can lead to cirrhosis and hepatocellular carcinoma. However, the rate of progression to cirrhosis and tumorigenesis in AH is greater than that in NASH. We asked whether there are differences between the two conditions in the expression levels of proteins involved in the pathogenesis of hepatocellular carcinoma. The proteins tested were presented at the 2017 American Association for the Study of Liver Diseases (AASLD) Liver Meeting as overexpressed in hepatocellular carcinoma: KLF4, SCL19A1, FANCG, HRH-1, DNMT1, DNMT3B, TNFR2, DUSP4, EGFR, Integrin α6, HDACII, PDE3A, BCL-XL, and MTCO2. The expression of these proteins was measured in liver biopsy sections from NASH and AH patients using immunohistochemical staining with fluorescent antibodies and then quantifying the fluorescence intensity morphometrically. In AH patients, levels of all tested proteins except HRH-1 were elevated compared to normal patients. In NASH patients, KLF4, SCL19A1, FANCG, HDACII, BCL-XL levels were increased compared to normal controls while HRH-1, DNMT1 and PDE3A levels were decreased. The relative expression of all proteins studied except BCL-XL was significantly higher in AH compared to NASH. In conclusion, proteins involved in hepatocellular cancer development are more highly expressed in AH compared to NASH and normal liver, which corresponds with the higher rate of tumorigenesis in AH patients compared to NASH patients.
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