The molecular hallmarks and clinical consequences of tumor hypoxia in prostate cancer.

81Background: Localised prostate cancers are classified into risk-groups using clinical measurements like grade and stage to inform treatment decisions. However, these groupings are imprecise: ~30% of intermediate-risk patients suffer relapse of their disease despite precision image-guided radiotherapy or radical prostatectomy. One reason for this variability in response to treatment is the underlying cellular and molecular heterogeneity of tumours. Prostate tumour cells exist within a microenvironment characterized by gradients of oxygen levels and prostate tumours with low levels of oxygen (hypoxia) have poor clinical outcomes. Methods: Hypoxia was measured using multiple mRNA-based signatures. We examined 548 patients with localised prostate cancer and statistically assessed the association of hypoxia with copy-number alterations (CNAs), single-nucleotide variants (SNVs), genomic rearrangements, focal genomic events (i.e. kataegis, chromothripsis), telomere length, clinical indices (i.e. grade, stage) ...