Introduction: Imaging genomics, a newly emerging field, links genomic information with specific imaging phenotypes. Predictive algorithms can then be used to non-invasively assess and follow the genomic cancer composition. Cell death in GBM is not completely understood; and, mechanisms such as rapid cellular proliferation-induced necrosis or autophagy (lack of nutrients/oxygen) and/or apoptosis are proposed. In this study, we identify a significant GBM necrosis gender bias and a potentially distinct mechanism of cell death in male versus female patients.
Methods: Using data obtained from The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA), gene expression, microRNA, and quantitative MR-imaging data sets were generated based on a total of 99 patients. The top concordant genes and microRNAs that correlated with the degree of cell death (MRI- derived “necrosis” volumes) were further analyzed using Ingenuity Pathway Analysis, and cognate microRNA-gene networks were created. The findings were replicated using a histopathology-genomic data set.
Results: Female patients demonstrated significantly lower volumes of cell death than male patients (P=0.03). Gender specific analysis revealed that female patients with high volumes of cell death on MRI had significantly shorter survival times (P=0.01). This difference was not observed in males (P=0.6). Genomic transcription factor analysis suggested that cell death in female GBM patients is driven by oncogenic MYC, while cell death in male GBM patients is rather induced by TP53 activity.
Conclusions: This is knowingly the first report in the literature to suggest that GBM cell death may be driven by gender-specific molecular pathways. The gender bias was significant and concordant on MRI, histopathology, and survival phenotype levels. These data suggest a potential gender-specific biology and may lead to targeted gender-genomic GBM therapies.
Patient Care: Understanding that gender has a significant effect on molecular pathways can lead to novel cancer therapeutics and will advance personalized medicine.
Learning Objectives: Gender-Genomics in Glioblastoma can be a novel field of research, which may lead to novel therapeutics targeting distinct molecular pathways in male versus female patients.