RT Journal Article
SR Electronic
T1 Clinically Important sex differences in GBM biology revealed by analysis of male and female imaging, transcriptome and survival data
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 232744
DO 10.1101/232744
A1 Wei Yang
A1 Nicole M. Warrington
A1 Sara J. Taylor
A1 Eduardo Carrasco
A1 Kyle W. Singleton
A1 Ningying Wu
A1 Justin D. Lathia
A1 Michael E. Berens
A1 Albert H. Kim
A1 Jill S. Barnholtz-Sloan
A1 Kristin R. Swanson
A1 Jingqin Luo
A1 Joshua B Rubin
YR 2017
UL http://biorxiv.org/content/early/2017/12/12/232744.abstract
AB Sex differences in the incidence and outcome of human disease are broadly recognized but in most cases not adequately understood to enable sex-specific approaches to treatment. Glioblastoma (GBM), the most common malignant brain tumor, provides a case in point. Despite well-established differences in incidence, and emerging indications of differences in outcome, there are few insights that distinguish male and female GBM at the molecular level, or allow specific targeting of these biological differences. Here, using a quantitative imaging-based measure of response, we found that temozolomide chemotherapy is more effective in female compared to male GBM patients. We then applied a novel computational algorithm to linked GBM transcriptome and outcome data, and identified novel sex-specific molecular subtypes of GBM in which cell cycle and integrin signaling were identified as the critical determinants of survival for male and female patients, respectively. The clinical utility of cell cycle and integrin signaling pathway signatures was further established through correlations between gene expression and in vitro chemotherapy sensitivity in a panel of male and female patient-derived GBM cell lines. Together these results suggest that greater precision in GBM molecular subtyping can be achieved through sex-specific analyses, and that improved outcome for all patients might be accomplished via tailoring treatment to sex differences in molecular mechanisms.One Sentence Summary Male and female glioblastoma are biologically distinct and maximal chances for cure may require sex-specific approaches to treatment.