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

Research output: Contribution to journalArticle

12 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

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'High levels of phosphorylated MAP kinase are associated with poor survival among patients with glioblastoma during the temozolomide era'. Together they form a unique fingerprint.

  • 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