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

Rongxuan Hua; Qiuxuan Li; Han Gao; Boya Wang; Chengwei He; Ying Wang; Sitian Zhang; Lei Gao; Hongwei Shang; Wen Wang; Jingdong Xu

doi:10.4103/jrms.jrms_371_22

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

J Res Med Sci. 2023 Jun 12:28:47. doi: 10.4103/jrms.jrms_371_22. eCollection 2023.

Authors

Rongxuan Hua¹, Qiuxuan Li¹, Han Gao², Boya Wang³, Chengwei He², Ying Wang⁴, Sitian Zhang¹, Lei Gao⁵, Hongwei Shang⁶, Wen Wang⁷, Jingdong Xu²

Affiliations

¹ Department of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
² Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
³ Undergraduate Student of 2018 Eight Program of Clinical Medicine, Peking University People's Hospital, Beijing, China.
⁴ Department of Dermatology, Beijing Tong Ren Hospital, Capital Medical University, Beijing, China.
⁵ Department of Bioinformatics, College of Bioengineering, Capital Medical University, Beijing, China.
⁶ Experimental Center for Morphological Research Platform, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
⁷ Department of Experimental Animal Research, Xuan Wu Hospital, Capital Medical University, Beijing, China.

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.

Publication types

Review