Dynamic alteration of telomerase expression and its diagnostic significance in liver or peripheral blood for hepatocellular carcinoma

AIM： To investigate the dynamic alteration of telomerase expression during development of hepatocellular carcinoma （HCC） and its diagnostic implications in liver tissues or peripheral blood mononuclear cells for HCC. METHODS： Dynamic expressions of liver telomerase during malignant transformation of hepatocytes were observed in Sprague-Dawly （SD） rats fed with 0.05% of 2-fluoenyacetamide （2-FAA）. Total RNA and telomerase were extracted from rat or human liver tissues. The telomerase activities in livers and in circulating blood were detected by a telomeric repeat amplification protocol-enzyme-linked immunosorbent assay （TRAP- ELISA）, and its diagnostic value was investigated in patients with benign or malignant liver diseases. RESULTS： The hepatoma model displayed the dynamic expression of hepatic telomerase during HCC development. The telomerase activities were consistent with liver total RNA levels （r = 0.83, P 〈 0.01） at the stages of degeneration, precancerosis, and cancerization of hepatocytes. In HCC patients, the telomerase levels in HCC tissues were significantly higher than in their adjacent non-cancerous tissues, but liver total RNA levels were lower in the former than in the latter. Although the circulating telomerase of HCC patients was abnormally expressed among patients with chronic liver diseases, the telomerase activity was a non-specific marker for HCC diagnosis, because the incidence was 15.7% in normal control, 25% in chronic hepatitis, 45.9% in liver cirrhosis, and 85.2% in HCC, respectively when absorbance value of telomerase activity was more than 0.2. If the value was over 0.6, the incidence was 60% in HCC group and 0% in any of the others （P 〈 0.01） except in two cases with liver cirrhosis. However, the combination of circulating telomerase with serum alpha-fetoprotein level could increase the positive rate and the accuracy （92.6%, 125 of 135） of HCC diagnosis. CONCLUSION： The overexpression of telomerase is associated with HCC development, and its abnormality in liver tissues or in peripheral blood could be a useful marker for diagnosis and prognosis of HCC.

瞄准：在肝纸巾或外部血在肝细胞癌(HCC ) 和它的诊断含意的开发期间调查 telomerase 表示的动态改变为 HCC 的单音的原子房间。方法：肝 telomerase 的动态表情在 hepatocytes 的恶意的转变期间被观察在(SD ) Sprague-Dawly，老鼠用 0.05% 2-fluoenyacetamide (2-FAA ) 喂了。全部的 RNA 和 telomerase 从老鼠或人的肝纸巾被提取。在肝并且在传播的血的 telomerase 活动被 telomeric 重复扩大 protocol-enzyme-linked 免疫吸着剂试金(TRAP-ELISA ) 检测，并且它的诊断价值与良性或恶意的肝疾病在病人被调查。结果：肝细胞瘤模型在 HCC 开发期间显示了肝的 telomerase 的动态表示。telomerase 活动与肝总数 RNA 层次一致(r = 0.83， P<0.01 ) 在 hepatocytes 的退化，初癌状态，和癌化的阶段。在 HCC 病人，在 HCC 纸巾的 telomerase 层次比在他们的邻近的非癌的纸巾，而是肝全部的 RNA 铺平显著地高比在后者在前者是更低的。尽管 HCC 病人的传播 telomerase 反常地与长期的肝疾病在病人之中被表示，因为发生在正常控制是15.7%， telomerase 活动是为 HCC 诊断的一个非特定的标记，25%在长期的肝炎，45.9%在肝肝硬化，并且85.2%在 HCC ，分别地吸收度什么时候 telomerase 活动珍视，是超过 0.2 。如果价值是超过 0.6，发生在 HCC 组是 60% 并且 0% 在除了在有肝的二种情况中的其它(P<0.01 ) 的任何东西肝硬化。然而，有浆液 alpha-fetoprotein 水平的传播 telomerase 的联合能增加积极的率和精确性(92.6% ， 135 中的 125 个) HCC 诊断。结论：过去 telomerase 的表示在肝纸巾与 HCC 开发，和它的反常被联系或在外设，血能是为 HCC 的诊断和预后的一个有用标记。