Homeostatic status of thyroid hormones and brain water movement as determinant factors in biology of cerebral gliomas: a pilot study using a bioinformatics approach

Abstract

Introduction: The expression and localization of the water channel transporters, aquaporins (AQPs), in the brain are substantially modified in gliomas during tumorigenesis, cell migration, edema formation, and resolution. We hypothesized that the molecular changes associated with AQP1 and AQP4 in the brain may potentially be anticancer therapeutic targets. To test this hypothesis, a bioinformatics analysis of publicly available data from international consortia was performed.

Methods: We used RNA-seq as an experimental strategy and identified the number of differential AQP1 and AQP4 transcript expressions in glioma tissue compared to normal brain tissue.

Results: AQPs genes are overexpressed in patients with glioma. Among the glioma subtypes, AQP1 and AQP4 were overexpressed in astrocytoma (low-grade glioma) and classical (high-grade glioma). Overall survival analysis demonstrated that both AQP genes can be used as prognostic factors for patients with low-grade glioma. Additionally, we observed a correlation between the expression of genes involved in the 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 = geq 0.20 and p-value = ≤ 0.05).

Conclusion: Our findings indicate that the thyroid hormone pathways and AQPs 1 and 4 are potential targets for new anti-tumor drugs and therapeutic biomarkers for malignant gliomas.

Keywords: AQPs; biomarkers; correlation analysis; gene expression; gliomas; thyroid hormones; water movement.