Detection of Telomerase Reverse Transcriptase mRNA in Peripheral Blood Mononuclear Cells of Patients With Liver Failure

Abstract

Background:Telomerase activity is closely associated with the expression of human telomerase reverse transcriptase (hTERT) mRNA; although it can be induced in hepatocytes during liver regeneration, its dynamic change in patients with liver failure has remained unclear.Objectives:We investigated the variation and significance of hTERT mRNA expression in peripheral blood mononuclear cells (PBMCs) of the patients with liver failure.Patients and Methods:In this clinical experimental study, 76 Chinese patients were enrolled in the study between 2010 and 2012. The level of PBMCs hTERT mRNA was detected by relative quantitative real-time polymerase chain reaction (RT-PCR) in the samples taken before treatment and at seven-day intervals during a 28-day treatment period. The patients were divided into survivor and non-survivor groups according to the 3-months mortality after treatment. The dynamic variation of PBMCs hTERT mRNA was analyzed and its association with prognosis was assessed by the area under the receiver-operating characteristic curve.Results:The median level of PBMCs hTERT mRNA in survivors increased with treatment time and was significantly higher than the corresponding level in non-survivors after 14 days of treatment (P < 0.001). Subgroup analyses showed that the levels of PBMCs hTERT mRNA were remarkably higher in patients with acute-on-chronic liver failure than in those with chronic liver failure (P < 0.05). In patients with the same clinical type of liver failure, the level was markedly higher in survivors than in non-survivors after 14 days of treatment (P < 0.05); however, the levels were not significantly different between subgroups with different clinical type but the same prognosis. The sensitivity and specificity of PBMCs hTERT mRNA was high in evaluating the prognosis at day 14 and became much higher at days 21 and 28 post treatment. The expression of PBMCs hTERT mRNA had high sensitivity and specificity in evaluating the prognosis as early as day 14 post treatment and was significantly superior to the prognostic value of serum alpha-fetoprotein.Conclusions:The expression of PBMCs hTERT mRNA is closely associated with patient outcome, which indicates that hTERT mRNA in PBMCs might be useful as a prognostic biomarker of liver failure.

Radiosensitization to X-ray radiation by telomerase inhibitor MST-312 in human hepatoma HepG2 cells

“…Increasing studies reported that human telomerase reverse transcriptase (hTERT) was a telomerase catalytic subunit and served as the major limiting agent for telomerase activity [3,4,38]. Telomerase activity was closely associated with the expression of hTERT mRNA [3,4,8,22], therefore hTERT mRNA expression was quantified by real-time fluorescent quantitative PCR to reflect telomerase activity (Fig.…”

“…Telomerase activity was closely associated with the expression of hTERT mRNA [3,4,8,22], therefore hTERT mRNA expression was quantified by real-time fluorescent quantitative PCR to reflect telomerase activity (Fig. 2).…”