Zejnullahu Vjosa A, Zejnullahu Valon A, Josifovska Slavica, Vukovik Nikola, Pakovski Kiril, Panov Sasho
Department of Obstetrics and Gynecology, University Clinical Center of Kosovo, Pristina, Kosovo.
Department of Molecular Biology, Genetics and Microbiology, Institute of Biology, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University, Skopje, Republic of Macedonia.
Pril (Makedon Akad Nauk Umet Odd Med Nauki). 2017 Dec 1;38(3):143-151. doi: 10.2478/prilozi-2018-0015.
Telomerase Reverse Transcriptase (TERT) is the main catalytic sub-unit of telomerase, a reverse transcriptase enzyme. Telomerase expression is regulated at many levels, with numerous studies suggesting that up-regulation of human TERT gene (hTERT) at transcriptional level results in immortal cell phenotype associated with cancer. The aim of this study is to determine the correlation between hTERT expression and different cervical precursor lesions, as well as with cervical cancer in patients with confirmed Human papillomavirus (HPV) infection. The study included molecular analyzes on cervical samples from 214 women and matched Papanicolaou (Pap) test results. HPV detection and genotyping was performed by polymerase chain reaction (PCR) and genotyping. Quantitative real-time PCR (qRT-PCR) was performed using TaqMan probes and were calculated relative to the reference gene. Results showed significantly increased hTERT mRNA expression levels in high-grade and low-grade lesions compared to normal control samples (p<0.01) associated with 6.31 fold higher risk for developing ASC-US and 9.20 for LSIL. Strong correlation between HPV infection and hTERT expression in the high-grade lesions and cervical cancer was also observed. hTERT relative expression values showed 98% specificity and 100 % sensitivity as indicator of cervical lesions particularly for the ACS-H, HSIL and cervical cancer. In conclusion, hTERT expression correlate with the cytological grade of the cervical lesions and HPV infection and has a potential to be used as a diagnostic and prognostic marker.
端粒酶逆转录酶(TERT)是端粒酶的主要催化亚基,端粒酶是一种逆转录酶。端粒酶的表达在多个水平受到调控,众多研究表明,人类TERT基因(hTERT)在转录水平的上调会导致与癌症相关的细胞永生化表型。本研究的目的是确定hTERT表达与不同宫颈前体病变之间的相关性,以及与确诊感染人乳头瘤病毒(HPV)的患者的宫颈癌之间的相关性。该研究包括对214名女性宫颈样本的分子分析以及匹配的巴氏试验结果。通过聚合酶链反应(PCR)和基因分型进行HPV检测和基因分型。使用TaqMan探针进行定量实时PCR(qRT-PCR),并相对于参考基因进行计算。结果显示,与正常对照样本相比,高级别和低级别病变中的hTERT mRNA表达水平显著升高(p<0.01),发展为非典型鳞状细胞(ASC-US)的风险高6.31倍,发展为低度鳞状上皮内病变(LSIL)的风险高9.20倍。在高级别病变和宫颈癌中也观察到HPV感染与hTERT表达之间存在强相关性。hTERT相对表达值作为宫颈病变的指标,尤其是对于高级别鳞状上皮内病变(ACS-H)、高度鳞状上皮内病变(HSIL)和宫颈癌,显示出98%的特异性和100%的敏感性。总之,hTERT表达与宫颈病变的细胞学分级和HPV感染相关,有潜力用作诊断和预后标志物。