LRP1B deletion is associated with poor outcome for glioblastoma patients

J Neurol Sci. 2015 Nov 15;358(1-2):440-3. doi: 10.1016/j.jns.2015.09.345. Epub 2015 Sep 11.

Abstract

Introduction: Deletion of the tumor suppressor gene LRP1B has been reported in glioblastoma, the most aggressive primary brain tumor in adults. Our objective was to analyze frequency and prognostic impact of LRP1B deletion and expression levels.

Methods: We retrospectively included all the primary IDH1/2 wild-type GBM patients with available clinical follow-up, DNA and RNA from our database. Deletions were analyzed by SNP-array. LRP1B mRNA expression was analyzed by reverse transcription quantitative polymerase chain reaction.

Results: 178 patients were included with a median age of 62.36 years. LRP1B deletions were observed for 10.1% of patients (complete: 2.8%, partial: 7.3%). LRP1B deletions were associated with poor progression-free survival (PFS) (p=0.004) and overall survival (OS) (p=0.001). By multivariate analysis, LRP1B deletions remained significant for both PFS (p=0.003, hazard ratio (HR): 2.261) and OS (p=0.001, HR: 2.609). LRP1B was down expressed with a mean relative expression of 46% comparatively to normal tissue. No association between LRP1B mRNA and patient outcome was observed. No correlation was found between the deletions and the mRNA down-expression. These results were validated using GBM TCGA data.

Conclusion: LRP1B presents with frequent molecular alterations which impact patient outcome, highlighting the potential interest of this gene for glioblastoma patients.

Keywords: Deletion; Expression; Glioblastoma; LRP1B; Prognostic; SNP-array.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / radiotherapy
  • Disease-Free Survival
  • Female
  • Gene Deletion
  • Gene Expression
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics*
  • Glioblastoma / radiotherapy
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Polymorphism, Single Nucleotide
  • Receptors, LDL / genetics*
  • Retrospective Studies
  • Young Adult

Substances

  • LRP1B protein, human
  • Receptors, LDL