Association of human telomerase reverse transcriptase promoter mutation with unfavorable prognosis in glioma: A systematic review and meta-analysis

Abstract

Background: Glioma is one of the most malignant and aggressive tumors, with an extremely poor prognosis. Human telomerase reverse transcriptase (hTERT) promoter mutation is regarded as a risk factor in tumor growth. Although the prevalence of hTERT promoter (pTERT) mutation in gliomas has been investigated, the results are inconsistent. This meta-analysis aims to investigate the prognostic value of hTERT in glioma patients and its interaction with other biomarkers. Materials and Methods: We searched 244 citations from four databases: PubMed (2000–2021), Web of Science (2000–2021), Embase (2010–2021), and Cochrane Library (2000–2021) with 28 articles included. Results: We calculated hazard ratios (HRs) using the random effect model and the pooled result suggested that TERT promoter mutation predicted poorer overall survival (HR: 1.53, 95% confidence interval [CI]: 1.34–1.75, P < 0.001, I2: 49.9%, pheterogeneity:0.002) and progression-free survival (HR: 1.55, 95% CI: 1.27–1.88, P < 0.001, I2: 0.0%, pheterogeneity: 0.473). For subgroup analysis, we analyzed multiple factors including iso-citrate dehydrogenase (IDH) genotype, age, diagnosis, pTERT region, so as to locate the sources of heterogeneity. Interestingly, in IDH mutant subgroup, pTERT mutation became a beneficial prognostic factor (HR: 0.73, 95% CI: 0.57–0.93, I2: 22.3%, pheterogeneity: 0.277), which is contrary to the results in pooled analysis. Conclusion: In general, pTERT mutation may result in shorter survival time in glioma patients, but longer survival time when glioma patients are combined with IDH mutation.

Keywords

• glioma
• human telomerase reverse transcriptase
• iso-citrate dehydrogenase
• meta-analysis
• prognosis