Wu Wei, Yao Deng-Fu, Qiu Li-Wei, Wu Xin-Hua, Yao Ming, Su Xiao-Qin, Zou Li
Research Center of Clinical Molecular Biology, Affiliated Hospital, Nantong University, Nantong 226001, China.
Hepatobiliary Pancreat Dis Int. 2005 Nov;4(4):544-9.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. Telomerase is reactivated in various types of malignant tumors and may contribute to the development of HCC. To evaluate the role of telomerase in formation and development of HCC, we analyzed its expression status in different parts of HCC tissues and peripheral blood mononuclear cells (PBMCs), and explored its clinical implications for diagnosis of HCC.
Total RNAs and telomerase were extracted from HCC and their non-cancerous tissues, and both relationships were analyzed between them. The expression of telomerase reverse transcriptase (hTERT) mRNA and telomerase activities in liver tissues and PBMCs were detected by RT-PCR and telomeric repeat amplification protocol (TRAP)-ELISA, respectively. The diagnostic values of telomerase in PBMCs were investigated in the diagnosis and differentiation of HCC.
The specific activities of telomerase were 18.25+/-15.02 A/microg RNA in HCC tissues, and significantly higher than those in their non-cancerous tissues (8.16+/-6.22 A/microg RNA, P<0.05). But total RNA levels in HCC were 12.40+/-7.34 microg/mg wet liver and lower than 53.77+/-52.02 microg/mg wet liver in their non-cancerous parts (P<0.01). The different telomerase levels could be detected in PBMCs from patients with chronic liver diseases and control group. The enzyme activities were significantly higher in HCC than in any other groups (P<0.01). However, circulating telomerase levels were more obviously decreased in HCC patients after transcatheter arterial embolization treatment than before the treatment (P<0.01). The analysis of combined serum alpha-fetoprotein level and PBMCs telomerase was more sensitive and specific for the diagnosis of HCC.
The abnormal expression of telomerase in HCC tissues and circulating PBMCs could be a useful marker to the diagnosis and prognosis of HCC.
肝细胞癌（HCC）是全球最常见的恶性肿瘤之一。端粒酶在各种类型的恶性肿瘤中被重新激活，可能与HCC的发生发展有关。为了评估端粒酶在HCC形成和发展中的作用，我们分析了其在HCC组织不同部位和外周血单个核细胞（PBMCs）中的表达情况，并探讨其对HCC诊断的临床意义。
从HCC及其癌旁组织中提取总RNA和端粒酶，并分析两者之间的关系。分别采用逆转录-聚合酶链反应（RT-PCR）和端粒重复序列扩增法（TRAP）-酶联免疫吸附测定（ELISA）检测肝组织和PBMCs中端粒酶逆转录酶（hTERT）mRNA的表达及端粒酶活性。研究PBMCs中端粒酶在HCC诊断及鉴别诊断中的价值。
HCC组织中端粒酶的比活性为18.25±15.02 A/μg RNA，显著高于其癌旁组织（8.16±6.22 A/μg RNA，P<0.05）。但HCC中的总RNA水平为12.40±7.34 μg/mg湿肝，低于其癌旁组织的53.77±52.02 μg/mg湿肝（P<0.01）。慢性肝病患者和对照组的PBMCs中可检测到不同水平的端粒酶。HCC组的酶活性显著高于其他任何组（P<0.01）。然而，经导管动脉栓塞治疗后，HCC患者循环端粒酶水平较治疗前明显降低（P<0.01）。联合血清甲胎蛋白水平和PBMCs端粒酶分析对HCC诊断更敏感、特异。
HCC组织和循环PBMCs中端粒酶的异常表达可能是HCC诊断和预后的有用标志物。
