Expressão diferencial de aquaporinas 1 e 4 em gliomas humanos e hormônios tireoideanos como seus possíveis correguladores: uma abordagem de bioinformática

Abstract

In 2016 the World Health Organization (WHO) included molecular markers (genotypic expression) as important predictive factors for diagnostic of brain tumors. In the brain, the expression and localization of water channel transporters, aquaporins (AQPs), are substantially modified in gliomas during tumorigenesis, cell migration, edema formation and resolution. Therefore, we hypothesized that molecular changes associated with AQP1 and AQP4 in the brain may be potential anticancer therapeutic targets. Our research group, for instance, has already shown a modulating action of triiodothyronine (T3), the biologically active form of thyroid hormone, on the AQP4 expression in the developing nervous system and on GBM cells. To test it, a bioinformatic analysis from publicly available data from international consortia was carried out. Here, we used RNA-seq as an experimental strategy and identified the differential expression of AQP1 and AQP4 transcripts numbers in gliomas tissue if compared to normal brain tissues. Indeed, the AQPs genes were overexpressed in glioma patients. Among gliomas subtypes, AQP1 and AQP4 were overexpressed in astrocytoma (low gradeglioma) and classical (high grade-glioma). The overall survival analysis demonstrated us both AQP genes can be used as a prognostic factor for patients with low gradeglioma, confirming the results of previous studies and reinforcing their clinical value. We also observed a correlation between the expression of genes involved in tyrosine and thyroid hormone pathways and AQPs. Namely: PNMT, ALDH1A3, AOC2, HGDATP1B1, ADCY5, PLCB4, ITPR1, ATP1A3, LRP2, HDAC1, MED24, MTOR and ACTB1 (Spearman’s coefficient = ≥ 0.20 and p-value = ≤ 0.05). These molecular pathways and AQP1 and AQP4 genes may be used to study new anti-tumor drugs and the molecular diagnosis of gliomas because showing potential as diagnostic and therapeutic biomarkers for malignant gliomas.