CDKN2A (p16) mRNA decreased expression is a marker of poor prognosis in malignant high-grade glioma

Tumour Biol. 2015 Sep;36(10):7607-14. doi: 10.1007/s13277-015-3480-5. Epub 2015 Apr 29.

Abstract

Human high-grade glioma is heterogeneous in nature based on pathological and genetic profiling. Various tumour suppressor gene alterations are considered as prognostic markers in high-grade glioma. Gene expression of CDKN2A (p16) is used in various cancers as a prognostic biomarker along with methylation and deletion status of this gene. Expression levels of p16 mRNA were not studied as a biomarker in gliomas before. In this study, we have performed mRNA quantification analysis on 48 high-grade glioma tissues and checked for a possible prognostic role. The decreased expression of p16 mRNA in majority of the tumour tissues (57.1 %) was observed when compared to control tissues (P = 0.02). mRNA expression level was correlated with clinical variables also. p16 deletion status and BMI1 mRNA expression were also considered for comparison. p16 mRNA was negatively correlated with the BMI1 mRNA (P = <0.0001) but not with p16 deletion. p16 mRNA expression, midline shift in MRI and tumour type were able to predict patient survival in overall survival (OS) and progression-free survival (PFS). p16 mRNA could independently predict prognosis of OS (P = 0.0146) and PFS (P = 0.0305) in multivariate analysis. We have shown that p16 mRNA expression can act as an independent prognostic biomarker in high-grade glioma.

Keywords: Decreased expression; Gene expression; Glioma; p16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Child
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • DNA Methylation / genetics
  • Disease-Free Survival
  • Female
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Male
  • Middle Aged
  • Polycomb Repressive Complex 1 / genetics
  • Prognosis
  • RNA, Messenger / genetics*
  • Young Adult

Substances

  • BMI1 protein, human
  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • RNA, Messenger
  • Polycomb Repressive Complex 1