■水通道转运蛋白的表达和定位,水通道蛋白(AQP),在肿瘤发生过程中,大脑中的神经胶质瘤被大量修饰,细胞迁移,水肿形成,和决议。我们假设脑中与AQP1和AQP4相关的分子变化可能是潜在的抗癌治疗靶标。为了检验这个假设,对国际财团的公开数据进行了生物信息学分析。
■我们使用RNA-seq作为实验策略,并鉴定了与正常脑组织相比,神经胶质瘤组织中差异AQP1和AQP4转录表达的数量。
■AQPs基因在神经胶质瘤患者中过度表达。在神经胶质瘤亚型中,AQP1和AQP4在星形细胞瘤(低级别神经胶质瘤)和经典(高级别神经胶质瘤)中过表达。总体生存分析表明,两种AQP基因均可作为低级别胶质瘤患者的预后因素。此外,我们观察到参与酪氨酸和甲状腺激素途径的基因表达与AQPs之间的相关性,即:PNMT,ALDH1A3,AOC2,HGDATP1B1,ADCY5,PLCB4,ITPR1,ATP1A3,LRP2,HDAC1,MED24,MTOR,和ACTB1(斯皮尔曼系数=geq0.20,p值=≤0.05)。
■我们的发现表明,甲状腺激素途径和AQPs1和4是新的抗肿瘤药物和恶性神经胶质瘤治疗性生物标志物的潜在靶标。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.