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.
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【Dynamic alteration of telomerase expression and its diagnostic significance in liver or peripheral blood for hepatocellular carcinoma.].
【肝细胞癌肝或外周血端粒酶表达的动态变化及其诊断意义。】
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DOI：10.3748/wjg.v12.i31.4966文章类型：杂志文章
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目的：研究肝细胞癌（HCC）发展过程中端粒酶表达的动态变化及其在肝组织或外周血单核细胞中的诊断意义。
方法：在喂食0.05％2-氟乙酰胺（2-FAA）的Sprague-Dawly（SD）大鼠中观察肝细胞恶性转化过程中肝端粒酶的动态表达。从大鼠或人肝脏组织中提取总RNA和端粒酶。通过端粒重复扩增方案-酶联免疫吸附测定（TRAP-ELISA）检测肝脏和循环血液中的端粒酶活性，并对其在良性或恶性肝病患者中的诊断价值进行研究。
结果：肝癌模型在肝癌发生过程中表现出肝端粒酶的动态表达。在变性，癌前期和肝细胞癌化阶段，端粒酶活性与肝脏总RNA水平一致（r = 0.83，P <0.01）。在HCC患者中，HCC组织中的端粒酶水平显着高于其相邻的非癌组织，但前者的肝脏总RNA水平低于后者。尽管在慢性肝病患者中HCC患者的循环端粒酶异常表达，但端粒酶活性不是HCC诊断的非特异性标志物，因为正常对照组的发生率为15.7％，慢性肝炎为25％，肝为45.9％当端粒酶活性的吸光度值大于0.2时，肝硬化和HCC中的85.2％。如果该值超过0.6，则除两名肝硬化患者外，HCC组的发生率为60％，其他任何一组的发生率为0％（P <0.01）。但是，循环端粒酶与血清甲胎蛋白水平的结合可以提高HCC诊断的阳性率和准确率（92.6％，第125页）。
结论：端粒酶的过表达与肝癌的发生有关，其在肝组织或外周血中的异常可能是诊断和预后的有用标志物。
方法：在喂食0.05％2-氟乙酰胺（2-FAA）的Sprague-Dawly（SD）大鼠中观察肝细胞恶性转化过程中肝端粒酶的动态表达。从大鼠或人肝脏组织中提取总RNA和端粒酶。通过端粒重复扩增方案-酶联免疫吸附测定（TRAP-ELISA）检测肝脏和循环血液中的端粒酶活性，并对其在良性或恶性肝病患者中的诊断价值进行研究。
结果：肝癌模型在肝癌发生过程中表现出肝端粒酶的动态表达。在变性，癌前期和肝细胞癌化阶段，端粒酶活性与肝脏总RNA水平一致（r = 0.83，P <0.01）。在HCC患者中，HCC组织中的端粒酶水平显着高于其相邻的非癌组织，但前者的肝脏总RNA水平低于后者。尽管在慢性肝病患者中HCC患者的循环端粒酶异常表达，但端粒酶活性不是HCC诊断的非特异性标志物，因为正常对照组的发生率为15.7％，慢性肝炎为25％，肝为45.9％当端粒酶活性的吸光度值大于0.2时，肝硬化和HCC中的85.2％。如果该值超过0.6，则除两名肝硬化患者外，HCC组的发生率为60％，其他任何一组的发生率为0％（P <0.01）。但是，循环端粒酶与血清甲胎蛋白水平的结合可以提高HCC诊断的阳性率和准确率（92.6％，第125页）。
结论：端粒酶的过表达与肝癌的发生有关，其在肝组织或外周血中的异常可能是诊断和预后的有用标志物。
