Kasprzak Aldona, Adamek Agnieszka, Przybyszewska Wiesława, Olejniczak Karolina, Biczysko Wiesława, Mozer-Lisewska Iwona, Zabel Maciej
Department of Histology and Embryology, University of Medical Sciences, Poznań, Poland.
Folia Histochem Cytobiol. 2009 Jan;47(3):385-94. doi: 10.2478/v10042-009-0096-x.
Studies indicate that proteins of hepatitis C virus (HCV) disturb expression of cell-cycle-related proteins. A disturbed cell-cycle control is a hepatocellular carcinoma (HCC) risk factor in patients with HCV-related liver damage. The present study aimed to analyse the cellular expression of p21/Wafl/Cipl (p21) in long-lasting chronic hepatitis C (CH-C), its correlation with the key oncogenic HCV proteins (C, NS3, NS5A), other cell-cycle-related proteins (PCNA, Ki-67, cyclin D1, p53) and selected clinical data. Archival liver biopsies, obtained from patients with CH-C, normal livers, and hepatocellular carcinoma (HCC) specimens were analysed by immunocytochemistry and ImmunoMax technique. In CH-C overexpression of p21 protein was demonstrated. Positive correlations of p21 protein expression in CH-C involved age of the patients, grading, and liver steatosis. Moreover, expression of p21 correlated significantly with expression of p53 protein, of D1 cyclin and Ki-67. Although Ki-67 antigen was related to p21 expression, only Ki-67 expression proved to be directly related to liver staging. Expression of the NS3 protein, which prevailed in CH-C patients, manifested correlation with p21 expression, and that of cyclin D1. In presence of preserved potential for regeneration, overexpression of p21 indicates inhibition of cell cycle in hepatocytes, which probably plays a protective role for the chronically damaged cells. Out of the three HCV proteins only NS3 seems to affect control of p21 protein expression in in vivo infection. Nevertheless, the studies indicate that neither expression of p21 protein nor that of viral NS3 protein can serve as a marker of progression of CH-C to HCC in vivo.
研究表明，丙型肝炎病毒（HCV）的蛋白质会干扰细胞周期相关蛋白质的表达。细胞周期控制紊乱是HCV相关肝损伤患者发生肝细胞癌（HCC）的危险因素。本研究旨在分析持久慢性丙型肝炎（CH-C）中p21/Wafl/Cipl（p21）的细胞表达情况，及其与关键致癌HCV蛋白（C、NS3、NS5A）、其他细胞周期相关蛋白（PCNA、Ki-67、细胞周期蛋白D1、p53）以及选定临床数据的相关性。通过免疫细胞化学和ImmunoMax技术对取自CH-C患者、正常肝脏和肝细胞癌（HCC）标本的存档肝活检组织进行分析。结果显示CH-C中p21蛋白过表达。CH-C中p21蛋白表达与患者年龄、分级及肝脂肪变性呈正相关。此外，p21的表达与p53蛋白、细胞周期蛋白D1和Ki-67的表达显著相关。虽然Ki-67抗原与p21表达有关，但只有Ki-67的表达被证明与肝脏分期直接相关。在CH-C患者中占主导的NS3蛋白的表达与p21表达及细胞周期蛋白D1的表达相关。在存在保留的再生潜能的情况下，p21的过表达表明肝细胞中细胞周期受到抑制，这可能对慢性受损细胞起到保护作用。在三种HCV蛋白中，只有NS3似乎在体内感染中影响p21蛋白表达的控制。然而，研究表明，无论是p21蛋白的表达还是病毒NS3蛋白的表达都不能作为CH-C在体内进展为HCC的标志物。
