Abstract
Background. Glioblastoma exhibits aggressive growth and poor outcomes despite treatment, and its marked var- iability renders therapeutic design and prognostication challenging. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling of 206 glio- blastoma patients, providing opportunities to identify novel associations between molecular features and clinical outcomes.
Methods. Survival analyses were performed using the Logrank test, and clinical features were evaluated using Wilcoxon and chi-squared tests with q-values derived via Benjamini-Hochberg correction. Mutational analyses util- ized sample-level enrichments from whole exome sequencing data, and statistical tests were performed using the one-sided Fisher Exact test with Benjamini-Hochberg correction. Transcriptomic analyses utilized a student’s t-test with Benjamini-Hochberg correction. Expression fold changes were processed with Ingenuity Pathway Analysis to determine pathway-level alterations between groups.
Results. Key findings include an association of MUC17, SYNE1, and TENM1 mutations with prolonged overall sur- vival (OS); decreased OS associated with higher epithelial growth factor receptor (EGFR) mRNA expression, but not with EGFR amplification or mutation; a 14-transcript signature associated with OS > 2 years; and 2 transcripts associated with OS < 1 year.
Conclusions Herein, we report the first clinical, genomic, and transcriptomic analysis of ORIEN glioblastoma cases, incorporating sample reclassification under updated 2021 diagnostic criteria. These findings create multiple av- enues for further investigation and reinforce the value of multi-institutional consortia such as ORIEN in deepening our knowledge of intractable diseases such as glioblastoma.
Document Type
Article
Publication Date
2024
Digital Object Identifier (DOI)
https://doi.org/10.1093/noajnl/vdae04
Repository Citation
Demetriou, Alexandra N.; Chow, Frances; Craig, David W.; Webb, Michelle G.; Ormond, D. Ryan; Battiste, James; Chakravarti, Arnab; Colman, Howard; Villano, John L.; Schneider, Bryan P.; Liu, James K. C.; Churchman, Michelle L.; and Zada, Gabriel, "Profiling the molecular and clinical landscape of glioblastoma utilizing the Oncology Research Information Exchange Network brain cancer database" (2024). Markey Cancer Center Faculty Publications. 210.
https://uknowledge.uky.edu/markey_facpub/210
Notes/Citation Information
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https:// creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.