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Research Paper|Volume 16, Issue 6|pp 5618—5633

Predicting the prognosis of glioma patients with TERT promoter mutations and guiding the specific immune profile of immune checkpoint blockade therapy

Wenpeng Cao1,2, Jinzhi Lan3, Chujiao Hu4,5,6, Jinping Kong4, Limin Xiang4, Zhixue Zhang4, Yating Sun4, Zhirui Zeng4, Shan Lei4
  • 1Department of Anatomy, School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou 550025, China
  • 2Key Laboratory of Human Brain Bank for Functions and Diseases of Department of Education of Guizhou, Guizhou Medical University, Guiyang, Guizhou 550025, China
  • 3Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University, Guiyang, Guizhou 550004, China
  • 4Department of Physiology, School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou 550025, China
  • 5State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550025, China
  • 6Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guiyang, Guizhou 550025, China
* Equal contribution
Received: September 1, 2023Accepted: December 26, 2023Published: March 18, 2024
https://doi.org/10.18632/aging.205668

Copyright: © 2024 Cao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The telomerase reverse transcriptase promoter (TERTp) is frequently mutated in gliomas. This study sought to identify immune biomarkers of gliomas with TERTp mutations. Data from TCGA were used to identify and validate survival-associated gene signatures, and immune and stromal scores were calculated using the ESTIMATE algorithm. High stromal or immune scores in patients with TERTp-mutant gliomas correlated with shorter overall survival compared to cases with low stromal or immune scores. Among TERTp-mutant gliomas with both high immune and high stromal scores, 213 commonly shared DEGs were identified. Among 71 interacting DEGs representing candidate hub genes in a PPI network, HOXC6, WT1, CD70, and OTP showed significant ability in establishing subgroups of high- and low-risk patients. A risk model based on these 4 genes showed strong prognostic potential for gliomas with mutated TERTp, but was inapplicable for TERTp-wild-type gliomas. TERTp-mutant gliomas with high-risk scores displayed a greater percentage of naïve B cells, plasma cells, naïve CD4 T cells, and activated mast cells than low-risk score gliomas. TIDE analysis indicated that immune checkpoint blockade (ICB) therapy may benefit glioma patients with TERTp mutations. The present risk model can help predict prognosis of glioma patients with TERTp mutations and aid ICB treatment options.