mRNA quantification and clinical evaluation of telomerase reverse transcriptase subunit (hTERT) in intracranial tumours of patients in the island of Crete

Abstract

Telomerase is a reverse transcriptase that maintains telomeres by adding telomeric TTAGGG repeats to the ends of human chromosomes. The aim of this study was to evaluate quantitatively the mRNA expression of telomerase catalytic subunit (hTERT) in different types of intracranial tumours in relation to their histologic pattern and grade and correlate it with progression-free (PFS) and overall survival (OS) of patients. Human telomerase reverse transcriptase mRNA levels were estimated by the use of real time RT -PCR in 68 samples of intracranial tumours. It revealed statistical correlation between hTERT mRNA expression levels and the grade of the tumours (Po0.001). Patients having negative expression of hTERT mRNA had statistically longer PFS (P ¼ 0.031) and OS (P ¼ 0.047). Cox univariate regression analysis revealed that hTERT mRNA-positive patients had a high and statistically significant risk of relapse (hazard ratio (HR) of 2.24 and P ¼ 0.038). In the Cox multivariate regression model, the levels of hTERT mRNA were adjusted for tumour grade and patients age, and since there was statistically significant relationship between the levels of hTERT mRNA and the grade of the tumours (P ¼ 0.003 or P ¼ 0.006, respectively), hTERT mRNA levels could not be considered as an independent prognostic factor for PFS or OS.

Evaluation of combination gene therapy with PTEN and antisense hTERT for malignant glioma in vitro and xenografts

“…Recent evidence showed that telomerase activity and hTERT were considerably higher in the tissues of many different cancers than in normal tissues, and that hTERT mRNA was detectable in all tumor cells possessing telomerase activity [6][7][8][9]. Higher telomerase activity and higher levels of hTERT mRNA expression correlated significantly with poor prognosis [10,11]. The most recent and significant advances in this area demonstrated that the inhibition or down-regulation of hTERT expression could inhibit telomerase activity and prevent the malignant proliferation of tumor cells [12][13][14][15].…”