Mir-21-Sox2 axis delineates glioblastoma subtypes with prognostic impact

Pratheesh Sathyan, University of Texas MD Anderson Cancer Center
Pascal O. Zinn, University of Texas MD Anderson Cancer Center
Anantha L. Marisetty, University of Texas MD Anderson Cancer Center
Bin Liu, University of Texas MD Anderson Cancer Center
Mohamed M. Kamal, The British University in EgyptFollow
Sanjay K. Singh, University of Texas MD Anderson Cancer Center
Pierre Bady, Centre Hospitalier Universitaire Vaudois
Li Lu, University of Texas MD Anderson Cancer Center
Khalida M. Wani, University of Texas MD Anderson Cancer Center
Bethany L. Veo, University of Texas MD Anderson Cancer Center
Joy Gumin, University of Texas MD Anderson Cancer Center
Dina Hamada Kassem, University of Texas MD Anderson Cancer Center
Frederick Robinson, University of Texas MD Anderson Cancer Center
Connie Weng, University of Texas MD Anderson Cancer Center
Veerabhadran Baladandayuthapani, University of Texas MD Anderson Cancer Center
Dima Suki, University of Texas MD Anderson Cancer Center
Howard Colman, University of Texas MD Anderson Cancer Center
Krishna P. Bhat, University of Texas MD Anderson Cancer Center
Erik P. Sulman, University of Texas MD Anderson Cancer Center
Ken Aldape, University of Texas MD Anderson Cancer Center
Rivka R. Colen, University of Texas MD Anderson Cancer Center
Roel G.W. Verhaak, University of Texas MD Anderson Cancer Center
Zhimin Lu, University of Texas MD Anderson Cancer Center
Gregory N. Fuller, University of Texas MD Anderson Cancer Center
Suyun Huang, University of Texas MD Anderson Cancer Center
Frederick F. Lang, University of Texas MD Anderson Cancer Center
Raymond Sawaya, University of Texas MD Anderson Cancer Center
Monika Hegi, Centre Hospitalier Universitaire Vaudois
Sadhan Majumder, University of Texas MD Anderson Cancer Center

Document Type

Article

Publication Date

11-11-2015

Abstract

© 2015 the authors. Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here,wereport that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21-Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with ClassBtumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21-Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21-Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes.

This document is currently not available here.

Share

COinS