端粒酶表达的动态变化及其在肝细胞癌肝脏或外周血中的诊断意义

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

作者信息

Yao Deng-Fu, Wu Wei, Yao Min, Qiu Li-Wei, Wu Xin-Hua, Su Xiao-Qin, Zou Li, Yao Deng-Bing, Meng Xian-Yong

机构信息

Research Center of Clinical Molecular Biology, Affiliated Hospital, Nantong University, Nantong 226001, Jiangsu Province, China.

出版信息

World J Gastroenterol. 2006 Aug 21;12(31):4966-72. doi: 10.3748/wjg.v12.i31.4966.

DOI:10.3748/wjg.v12.i31.4966

PMID:16937491

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4087398/

Abstract

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.

摘要

目的

研究端粒酶在肝细胞癌（HCC）发生发展过程中的动态变化及其在HCC肝组织或外周血单个核细胞中的诊断意义。

方法

用0.05%的2-氟乙酰胺（2-FAA）喂养Sprague-Dawly（SD）大鼠，观察肝细胞恶性转化过程中肝脏端粒酶的动态表达。从大鼠或人肝组织中提取总RNA和端粒酶。采用端粒重复序列扩增法-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，并研究其在良性或恶性肝脏疾病患者中的诊断价值。

结果

肝癌模型显示了HCC发生发展过程中肝脏端粒酶的动态表达。在肝细胞变性、癌前病变和癌变阶段，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组织中端粒酶水平显著高于其相邻的非癌组织，但前者肝脏总RNA水平低于后者。虽然HCC患者的循环端粒酶在慢性肝病患者中异常表达，但端粒酶活性是HCC诊断的非特异性标志物，因为当端粒酶活性吸光度值大于0.2时，正常对照组的发生率为15.7%，慢性肝炎组为25%，肝硬化组为45.9%，HCC组为85.2%。如果该值超过0.6，HCC组的发生率为60%，除两例肝硬化患者外，其他组均为0%（P<0.01）。然而，循环端粒酶与血清甲胎蛋白水平联合可提高HCC诊断的阳性率和准确性（92.6%，135例中的125例）。