Abstract：
The ATP1A3 gene is associated with the development and progression of neurological diseases. However, the pathological function and therapeutic value of ATP1A3 in glioblastoma (GBM) remains unknown. In this study, we tried to explore the correlation between the ATP1A3 gene expression and immune features in GBM samples. We found that ATP1A3 gene expression levels showed significant negative correlation with immune checkpoints such as PD-L1, CTLA-4 and IDO1. Next, ATP1A3 gene expression levels showed significant negative correlation with the anti-cancer immune cell process, the immune score and stromal score. By grouping ATP1A3 expression levels, we found that that immunomodulator-related genes and tumor-associated immune cell effector gene expression levels were associated with lower ATP1A3 expression. In addition, immunotherapy prediction pathway activity and a majority of the anti-cancer immune cell process activity levels were also showed to be correlated with lower ATP1A3 gene expression. Further, nine prognostic factors were identified by prognostic analysis, and a GBM prognostic model (risk score) was established. We applied the model to the TCGA GBM training set sample and the GSE4412 validation set sample and found that patients in the high risk score subgroup had significantly shorter survival time, demonstrating the prognostic value and prognostic efficacy of the risk score. Furthermore, ATP1A3 overexpression has also been found to sensitize cancer cells to anti-PD-1 therapy. In conclusion, we showed that ATP1A3 is a highly promising treatment target in GBM and the risk score is an independent prognostic factor for cancer and can be used to help guide the prediction of survival time in patients with GBM.
摘要：
ATP1A3基因与神经系统疾病的发生发展有关。然而,ATP1A3在胶质母细胞瘤（GBM）中的病理功能和治疗价值尚不清楚。在这项研究中,我们试图探索GBM样本中ATP1A3基因表达与免疫特征之间的相关性。我们发现ATP1A3基因表达水平与PD-L1、CTLA-4和IDO1等免疫检查点呈显著负相关。接下来,ATP1A3基因表达水平与抗癌免疫细胞进程呈显著负相关,免疫评分和基质评分。通过对ATP1A3表达水平进行分组，我们发现,免疫调节剂相关基因和肿瘤相关免疫细胞效应基因表达水平与ATP1A3表达降低相关.此外,免疫疗法预测通路活性和大部分抗癌免疫细胞过程活性水平也显示与较低的ATP1A3基因表达相关.Further,通过预后分析确定了9个预后因素，并建立GBM预后模型(风险评分)。我们将该模型应用于TCGAGBM训练集样本和GSE4412验证集样本，发现高风险评分亚组患者的生存时间明显缩短，证明风险评分的预后价值和预后功效。此外，还发现ATP1A3过表达使癌细胞对抗PD-1疗法敏感。总之,我们发现ATP1A3是GBM中一个非常有前景的治疗靶点,风险评分是癌症的独立预后因素,可用于指导GBM患者生存时间的预测.
