Involvement of steroid hormones and their receptors in the progression of low-and high-grade gliomas
Résumé
Methods: We mined the transcriptomic and clinical data from public databasesto identify male-over-female differentially expressed genes and selected those associated with patient survival using univariate analysis, depending on the grade, and molecular status (IDHwild type/mutated; 1p19q codeleted/not). Then, the link between the expression levels (low or high) of steroid biosynthesis enzyme or receptors of interest and survival was studied using the log rank test. Finally, a functional analysis of gender-specific correlated genes was performed.
Results: Aromatase, androgen and especially membrane estrogen receptor expressions were associated with patient survival and their correlated genes were mainly related to angiogenesis or immune response.Moreover, HOX-related genes appeared to be differentially expressed between males and femalesin low grade gliomasuggesting that these tumorscould originate in perturbation of developmental signals.
Conclusion: Therefore, consideration of the tight control of steroid hormone production and signaling seems crucial for the understanding of glioma pathogenesis and emergence of future tailoredtherapies.