Nucleoporin 88 expression in hepatitis B and C virus-related liver diseases

AIM: To investigate the expression of nucleoporin 88 (Nup88) in hepatitis B virus (HBV) and C virus (HCV)-related liver diseases. METHODS: We generated a new monoclonal Nup88 antibody to investigate the Nup88 protein expression by immunohistochemistry (IHC) in 294 paraffin-embedded liver specimens comprising all stages of hepatocellular carcinogenesis. In addition, in cell culture experiments HBV-positive (HepG2.2.15 and HB611) and HBV-negative (HepG2) hepatoma cell lines were tested for the Nup88 expression by Western-immunoblotting to test data obtained by IHC.RESULTS: Specific Nup88 expression was found in chronic HCV hepatitis and unspecific chronic hepatitis, whereas no or very weak Nup88 expression was detected in normal liver. The Nup88 expression was markedly reduced or missing in mild chronic HBV infection and inversely correlated with HBcAg expression. Irrespective of the HBV- or HCV-status, increasing Nup88 expression was observed in cirrhosis and dysplastic nodules, and Nup88 was highly expressed in hepatocellular carcinomas. The intensity of Nup88 expression significantly increased during carcinogenesis (P < 0.0001) and correlated with dedifferentiation (P < 0.0001). Interestingly, Nup88 protein expression was significantly downregulated in HBV-positive HepG2.2.15 (P < 0.002) and HB611 (P < 0.001) cell lines as compared to HBV-negative HepG2 cells. CONCLUSION: Based on our immunohistochemical data, HBV and HCV are unlikely to influence the expression of Nup88 in cirrhotic and neoplastic liver tissue, but point to an interaction of HBV with the nuclear pore in chronic hepatitis. The expression of Nup88 in nonneoplastic liver tissue might reflect enhanced metabolic activity of the liver tissue. Our data strongly indicate a dichotomous role for Nup88 in non-neoplastic and neoplastic conditions of the liver.

结直肠癌血清Nup88、CEA、CA19-9的表达及其临床意义

目的观察核孔蛋白88(Nup88)、癌胚抗原(CEA)及糖类抗原19-9(CA19-9)在结直肠(CRC)癌患者血清中的表达水平,探讨其临床意义。方法收集结直肠癌患者84例(CRC组)及正常对照组106例;采用化学发光法测定血清中CEA、CA19-9的表达,采用双抗体夹心ELISA法测定血清中Nup88蛋白的表达水平。结果 CRC组血清CEA及CA19-9蛋白的表达明显高于正常对照组(P<0.05);CRC组血清CEA及CA19-9的阳性率分别为46.43%和22.62%,明显高于对照组的5.66%和10.38%;且血清CEA的表达与CA19-9的表达呈显著正相关(r=0.459,P<0.01)。CRC组患者血清中Nup88的表达水平与CEA及CA19-9的表达无明显相关性(r分别为0.13,0.206,P>0.05)。结论结直肠癌患者血清Nup88、CEA及CA19-9的高表达对结直肠癌的临床诊断可能具有一定意义。

结直肠腺瘤中核孔蛋白88的表达及临床意义

目的:观察核孔蛋白88(Nucleoporin 88,Nup88)在结直肠腺瘤中的表达,分析其与临床病理特征间的关系。方法:采用SP免疫组织化学法检测163例结直肠腺瘤、43例结直肠癌和23例正常肠黏膜组织中Nup88蛋白的表达,统计学分析比较3组间Nup88蛋白表达的差异,及Nup88表达与结直肠腺瘤临床病理特征间的关系。结果:Nup88蛋白在正常黏膜组、结直肠腺瘤组及结直肠癌组的阳性表达率分别为0%,43.56%,55.81%,差异有统计学意义(P<0.01)。重度不典型增生的结直肠腺瘤中Nup88蛋白的阳性表达率明显高于轻、中度不典型增生者(60.71%vs 40%,P=0.044);Nup88的表达还与结直肠腺瘤的位置有关,腺瘤位于左半结肠及直肠者Nup88的表达明显高于右半结肠(P<0.017)。结论:Nup88在结直肠腺瘤中的高表达提示Nup88可能与结直肠癌的发生、发展有关。

结直肠癌中p53、Nup88的表达及其相关性

目的观察p53和Nup88在结直肠癌(CRC)中的表达,探讨二者相互作用的关系。方法采用逆转录聚合酶链反应(RT-PCR)分别检测结肠癌细胞株(HCT-116p53+/+和HCT-116p53-/-)中p53和Nup88 mRNA的表达,采用免疫组织化学法检测48例CRC及13例正常结直肠组织中p53和Nup88蛋白的表达。结果 HCT-116p53-/-细胞株中p53 mRNA的表达较HCT-116p53+/+明显下调,但Nup88 mRNA的表达在两者间无统计学差异;48例CRC中,p53和Nup88蛋白均呈高表达,阳性率分别为68.75%和72.92%,明显高于正常结直肠组织(P<0.01)。但未发现二者存在相关性(r=0.173,P>0.05)。结论 CRC中p53和Nup88蛋白均呈现高表达,二者均参与了结直肠癌的发生和发展,但未发现二者存在明显相关性。