Research Paper Volume 12, Issue 17 pp 17038—17061
A novel hypoxic tumor microenvironment signature for predicting the survival, progression, immune responsiveness and chemoresistance of glioblastoma: a multi-omic study
- 1 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China
Received: March 27, 2020 Accepted: June 22, 2020 Published: August 28, 2020https://doi.org/10.18632/aging.103626
How to Cite
Copyright: © 2020 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The hypoxic tumor microenvironment (TME) was reported to promote the aggressive phenotype, progression, recurrence, and chemoresistance of glioblastoma (GBM). We developed and validated a hypoxia gene signature for individualized prognostic prediction in GBM patients. In total, 259 GBM-specific hypoxia-related genes (HRGs) were obtained in hypoxic cultured GBM cells compared with normoxic cells. By applying the k-means algorithm, TCGA GBM patients were divided into two subgroups, and the patients in Cluster 1 exhibited high HRG expression patterns, older age, and poor prognosis, which was validated in the CGGA cohort. Cox regression analyses were performed to generate an HRG-based risk score model consisting of five HRGs, which could reliably discriminate the overall survival (OS) and progression-free survival (PFS) of high- and low-risk patients in both the TCGA training and CGGA validation cohorts. Then, nomograms with the hypoxia signature for OS and PFS prediction were constructed for individualized survival prediction, better treatment decision-making, and follow-up scheduling. Finally, functional enrichment, immune infiltration, immunotherapy response prediction and chemotherapy resistance analyses demonstrated the vital roles of the hypoxic TME in the development, progression, multitherpy resistance of GBM. The hypoxia gene signature could serve as a promising prognostic predictor and potential therapeutic target to combat chemoresistant GBM.