Allergy and inflammatory transcriptome is predominantly negatively correlated with CD133 expression in glioblastoma

Abstract

Allergies and the use of anti-inflammatory medication appear to be associated with reduced glioblastoma risk. However, these observations may merely reflect systemic immunosuppression induced by the tumor. To better understand the effect of this tumor on allergies and inflammation, we used CD133 mRNA expression as an indicator of tumor aggressiveness and systematically examined its relation to mRNA expression levels of 919 allergy- and inflammation-related genes in 142 glioblastoma tissue samples. We found that 69% of these genes are negatively correlated with CD133 expression including allergy-related (eg, interleukin [IL]-4R-αon correlation coefficient [r]5 20.40; 95% confidence interval [CI]5 20.53, 20.25) and immunoregulatory genes (eg, TGF-β20.35; 95% CI5 20.49, 20.20). Exceptions to this negative trend include the proinflammatory cytokine IL-17-β0.22; 95% CI 5 0.06, 0.37) and 2 IL-17 receptors. Also positively related to CD133 expression are NCAM-1 (r 5 0.45; 95% CI 5 0.31, 0.57) and PDGFR-a (r 5 0.45; 95% CI 5 0.30, 0.57). Previous literature suggests that NCAM-1+T cells infiltrate glioblastoma and may cause suppression of antitumor immunity, whereas PDGFR-α is involved in neurogenesis and amplified in glioblastoma. Ours is the first study to document downregulation of the majority of allergy- and inflammationrelated genes with glioblastoma progression. However, IL-17 and NCAM-1 may play proinflammatory and immunosuppressive roles, respectively, during the late stage of glioblastoma progression. Our findings suggest that immune function continues to change as the tumor progresses. © 2010 The Author(s).