Characterization of MGMT and EGFR protein expression in glioblastoma and association with survival Journal Article


Authors: Schaff, L. R.; Yan, D.; Thyparambil, S.; Tian, Y.; Cecchi, F.; Rosenblum, M.; Reiner, A. S.; Panageas, K. S.; Hembrough, T.; Lin, A. L.
Article Title: Characterization of MGMT and EGFR protein expression in glioblastoma and association with survival
Abstract: Purpose: Understanding the molecular landscape of glioblastoma (GBM) is increasingly important in the age of targeted therapy. O-6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation and EGFR amplification are markers that may play a role in prognostication, treatment, and/or clinical trial eligibility. Quantification of MGMT and EGFR protein expression may offer an alternative strategy towards understanding GBM. Here, we quantify baseline expression of MGMT and EGFR protein in newly diagnosed GBM samples using mass spectrometry. We correlate findings with MGMT methylation and EGFR amplification statuses and survival. Methods: We retrospectively identified adult patients with newly diagnosed resected GBM. MGMT and EGFR protein expression were quantified using a selected reaction monitoring mass spectrometry assay. Protein levels were correlated with MGMT methylation and EGFR amplification and survival data. Results: We found a statistically significant association between MGMT protein expression and promoter methylation status (p = 0.02) as well as between EGFR protein expression and EGFR amplification (p < 0.0001). EGFR protein expression and amplification were more tightly associated than MGMT protein expression and methylation. Only MGMT promoter methylation was statistically significantly associated with progression-free and overall survival. Conclusions: Unlike EGFR protein expression and EGFR amplification which are strongly associated, only a weak association was seen between MGMT protein expression and promoter methylation. Quantification of MGMT protein expression was inferior to MGMT methylation for prognostication in GBM. Discordance was observed between EGFR amplification and EGFR protein expression; additional study is warranted to determine whether EGFR protein expression is a better biomarker than EGFR amplification for clinical decisions and trial enrollment. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Keywords: adult; cancer survival; human tissue; protein expression; aged; major clinical study; overall survival; promoter region; cancer radiotherapy; temozolomide; multiple reaction monitoring; mass spectrometry; progression free survival; gene amplification; epidermal growth factor receptor; retrospective study; proteomics; correlation analysis; karnofsky performance status; quantitative analysis; glioblastoma; methylated dna protein cysteine methyltransferase; egfr; brain surgery; protein methylation; isocitrate dehydrogenase 1; mgmt; cancer prognosis; isocitrate dehydrogenase 2; very elderly; human; male; female; article
Journal Title: Journal of Neuro-Oncology
Volume: 146
Issue: 1
ISSN: 0167-594X
Publisher: Springer  
Date Published: 2020-01-01
Start Page: 163
End Page: 170
Language: English
DOI: 10.1007/s11060-019-03358-x
PUBMED: 31823165
PROVIDER: scopus
PMCID: PMC6939885
DOI/URL:
Notes: Article -- Export Date: 3 February 2020 -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Anne S Reiner
    248 Reiner
  2. Marc Rosenblum
    424 Rosenblum
  3. Katherine S Panageas
    512 Panageas
  4. Andrew Lee Lin
    61 Lin
  5. Lauren Rhea Schaff
    57 Schaff