High levels of phosphorylated MAP kinase are associated with poor survival among patients with glioblastoma during the temozolomide era

Chirag G. Patil, Miriam A Nuno, Adam Elramsisy, Debraj Mukherjee, Christine Carico, Jocelynn Dantis, Jethro Hu, John S. Yu, Xuemo Fan, Keith L. Black, Serguei I. Bannykh

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11 Scopus citations

Abstract

We investigated whether high levels of activated mitogen-activated protein kinase (p-MAPK) were associated with poor survival among patients with newly diagnosed glioblastoma during the temozolomide era. Nuclear p-MAPK expression of 108 patients with GBM was quantified and categorized in the following levels: low (0%-10%), medium (11%-40%), and high (41%-100%). Independent predictors of overall survival were determined using a multivariate Cox proportional hazards model. Our study included 108 patients with newly diagnosed GBM. Median age was 65 years, and 74% had high Karnofsky performance status (KPS ≥ 80). Median overall survival among all patients was 19.5 months. Activated MAPK expression levels of <10%, 11%-40%, and ≥41% were observed in 33 (30.6%), 37 (34.3%), and 38 (35.2%) patients, respectively. Median survival for low, medium, and high p-MAPK expression was 32.4, 18.2, and 12.5 months, respectively. Multivariate analysis showed 2.4-times hazard of death among patients with intermediate p-MAPK than low p-MAPK expression (hazard ratio [HR], 2.4; P =. 02); high-expression patients were 3.9 times more likely to die, compared with patients with low p-MAPK (HR, 3.9; P =. 007). Patients aged ≥65 years (HR, 2.8; P =. 002) with KPS < 80 (HR, 3.1; P =. 0003) and biopsy or partial resection (HR, 1.9; P =. 02) had higher hazard of death. MGMT and PTEN expression were not associated with survival differences. This study provides quantitative means of evaluating p-MAPK in patients with GBM. It confirms the significant and independent prognostic relevance of p-MAPK in predicting survival of patients with GBM treated in the temozolomide era and highlights the need for therapies targeting the p-MAPK oncogenic pathway.

Original languageEnglish (US)
Pages (from-to)104-111
Number of pages8
JournalNeuro-Oncology
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

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Keywords

  • EGFR
  • glioblastoma multiforme (GBM)
  • IDH1
  • MGMT
  • overall survival
  • p-MAPK
  • PTEN

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

Patil, C. G., Nuno, M. A., Elramsisy, A., Mukherjee, D., Carico, C., Dantis, J., Hu, J., Yu, J. S., Fan, X., Black, K. L., & Bannykh, S. I. (2013). High levels of phosphorylated MAP kinase are associated with poor survival among patients with glioblastoma during the temozolomide era. Neuro-Oncology, 15(1), 104-111. https://doi.org/10.1093/neuonc/nos272