Alexandra N Demetriou, Frances Chow, David W Craig, Michelle G Webb, D. Ormond, James Battiste, A. Chakravarti, H. Colman, J. Villano, Bryan P. Schneider, James K C Liu, Michelle L Churchman, Gabriel Zada
{"title":"Profiling the molecular and clinical landscape of glioblastoma utilizing the ORIEN brain cancer database","authors":"Alexandra N Demetriou, Frances Chow, David W Craig, Michelle G Webb, D. Ormond, James Battiste, A. Chakravarti, H. Colman, J. Villano, Bryan P. Schneider, James K C Liu, Michelle L Churchman, Gabriel Zada","doi":"10.1093/noajnl/vdae046","DOIUrl":null,"url":null,"abstract":"\n \n \n Glioblastoma exhibits aggressive growth and poor outcomes despite treatment, and its marked variability renders therapeutic design and prognostication challenging. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling of 206 glioblastoma patients, providing opportunities to identify novel associations between molecular features and clinical outcomes.\n \n \n \n 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 utilized 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.\n \n \n \n Key findings include an association of MUC17, SYNE1 and TENM1 mutations with prolonged overall survival (OS); decreased OS associated with higher EGFR mRNA expression, but not with EGFR amplification or mutation; a 14-transcript signature associated with OS >2 years; and two transcripts associated with OS <1 year.\n \n \n \n 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 avenues for further investigation and reinforce the value of multi-institutional consortia such as ORIEN in deepening our knowledge of intractable diseases such as glioblastoma.\n","PeriodicalId":3,"journal":{"name":"ACS Applied Electronic Materials","volume":"10 3","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Electronic Materials","FirstCategoryId":"0","ListUrlMain":"https://doi.org/10.1093/noajnl/vdae046","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, ELECTRICAL & ELECTRONIC","Score":null,"Total":0}
引用次数: 0
Abstract
Glioblastoma exhibits aggressive growth and poor outcomes despite treatment, and its marked variability renders therapeutic design and prognostication challenging. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling of 206 glioblastoma patients, providing opportunities to identify novel associations between molecular features and clinical outcomes.
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 utilized 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.
Key findings include an association of MUC17, SYNE1 and TENM1 mutations with prolonged overall survival (OS); decreased OS associated with higher EGFR mRNA expression, but not with EGFR amplification or mutation; a 14-transcript signature associated with OS >2 years; and two transcripts associated with OS <1 year.
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 avenues for further investigation and reinforce the value of multi-institutional consortia such as ORIEN in deepening our knowledge of intractable diseases such as glioblastoma.
期刊介绍:
ACS Applied Electronic Materials is an interdisciplinary journal publishing original research covering all aspects of electronic materials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials science, engineering, optics, physics, and chemistry into important applications of electronic materials. Sample research topics that span the journal's scope are inorganic, organic, ionic and polymeric materials with properties that include conducting, semiconducting, superconducting, insulating, dielectric, magnetic, optoelectronic, piezoelectric, ferroelectric and thermoelectric.
Indexed/Abstracted:
Web of Science SCIE
Scopus
CAS
INSPEC
Portico