Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma

CNS Neurosci Ther. 2020 Mar;26(3):297-308. doi: 10.1111/cns.13197. Epub 2019 Jul 18.

Abstract

Introduction: Glioblastoma (GBM) is the most lethal primary malignant brain tumor in adults with poor survival due to acquired therapeutic resistance and rapid recurrence. Currently, the standard clinical strategy for glioma includes maximum surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy; however, the median survival of patients with GBM remains poor despite these comprehensive therapies. Therefore, the identification of new prognostic biomarkers is urgently needed to evaluate the malignancy and long-term outcome of glioma.

Aims: To further investigate prognostic biomarkers and potential therapeutic targets for GBM.

Results: In this study, we identified tribbles pseudokinase 2 (TRIB2) as one of the genes that is most correlated with pathological classification, radioresistance, and TMZ resistance in glioma. Additionally, the expression of mitogen-activated protein kinase kinase kinase 1 (MAP3K1) showed a strong correlation with TRIB2. Moreover, a combined increase in TRIB2 and MAP3K1 was observed in GBM and indicated a poor prognosis of patients with glioma. Finally, enriched TRIB2 expression and MAP3K1 expression were shown to be associated with resistance to TMZ and radiotherapy.

Conclusion: Combined elevation of TRIB2 and MAP3K1 could be novel prognostic biomarkers and potential therapeutic targets to evaluate the malignancy and long-term outcomes of GBM.

Keywords: MAP3K1; TRIB2; glioblastoma; prognosis; therapy resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Calcium-Calmodulin-Dependent Protein Kinases / biosynthesis*
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / physiology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / drug therapy
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • MAP Kinase Kinase Kinase 1 / biosynthesis*
  • Male
  • Middle Aged
  • Prognosis
  • Temozolomide / therapeutic use*

Substances

  • Antineoplastic Agents, Alkylating
  • Calcium-Calmodulin-Dependent Protein Kinases
  • TRIB2 protein, human
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human
  • Temozolomide