Prognostic value of coexistence of abnormal expression of micro-RNA-200b and cyclic adenosine monophosphate-responsive element-binding protein 1 in human astrocytoma

Hum Pathol. 2014 Oct;45(10):2154-61. doi: 10.1016/j.humpath.2014.01.025. Epub 2014 May 8.

Abstract

Our aim was to investigate the expression of micro-RNA-200b (miR-200b) and cAMP-responsive element-binding protein 1 (CREB-1) in astrocytoma and its efficacy for predicting outcome. Both miR-200b and CREB-1 messenger RNA expression was measured in 122 astrocytomas and 30 nonneoplastic brain specimens by quantitative real-time polymerase chain reaction. Expression of miR-200b was significantly lower in astrocytoma than in nonneoplastic brain (P < .001), whereas CREB-1 messenger RNA expression was significantly elevated in the tumors (P < .001). Both miR-200b down-regulation and CREB-1 up-regulation were significantly associated with advanced pathologic grade (P = .002 and P = .006, respectively). Low miR-200b expression correlated negatively with Karnofsky performance score (P = .03), and high CREB-1 expression correlated positively with mean tumor diameter (P = .03). By Kaplan-Meier analysis, low miR-200b, high CREB-1, and coexistence of abnormal miR-200b and CREB-1 expression (low miR-200b/high CREB-1) were predictive of shorter progression-free survival and overall survival in both grade III and grade IV astrocytoma. By multivariate analysis, only low miR-200b/high CREB-1 expression was an independent prognostic factor for poor prognosis in astrocytoma of advanced grade. Both miR-200b and CREB-1 may play important cooperative roles in the progression of human astrocytoma. The efficacy of miR-200b and CREB-1 together as a predictor of prognosis in astrocytoma patients is shown for the first time.

Keywords: Astrocytoma; CREB-1; Micro-RNA-200b; Prognosis; Tumor progression.

MeSH terms

  • Aged
  • Astrocytoma / metabolism
  • Astrocytoma / mortality
  • Astrocytoma / pathology*
  • Biomarkers, Tumor / analysis
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology*
  • Cyclic AMP Response Element-Binding Protein / analysis
  • Cyclic AMP Response Element-Binding Protein / biosynthesis*
  • Disease Progression
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / analysis
  • MicroRNAs / biosynthesis*
  • Middle Aged
  • Prognosis
  • Real-Time Polymerase Chain Reaction

Substances

  • Biomarkers, Tumor
  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • MIRN200 microRNA, human
  • MicroRNAs