Quaking基因在胶质瘤组织中的表达及临床意义

【摘要】目的探究Quaking(QKI)基因在胶质瘤中的表达特征和预后相关性。方法联合使用中国脑胶质瘤基因组图谱和癌症基因组图谱计划探究QKI表达水平与胶质瘤患者WHO等级、年龄、IDH突变状态和染色体1p19q缺失的关系。然后比较QKI高、低表达组胶质瘤患者的总生存期之间的差异。使用功能富集分析探索QKI在生物学上的功能。应用TIMER分析QKI表达与胶质瘤免疫浸润细胞的关系。结果QKI在WHO Ⅳ级胶质瘤患者中的表达水平显著降低（P＜0.001）；QKI在IDH突变型、染色体1p19q杂合缺失型和年龄≤41岁胶质瘤中的表达水平较高（P＜0.001）；QKI高表达组的生存时间高于低表达组（P＜0.001），多因素COX回归模型分析结果显示，QKI高表达（P=0.038）是胶质瘤患者生存相关的独立影响因子；生物信息学分析结果显示，QKI相关表达基因功能主要富集在RNA剪接、细胞颗粒以及蛋白酶激活等生物学过程，与胶质瘤、ErbB和GnRH信号通路关系密切。在胶质瘤免疫微环境中，QKI与多种免疫浸润细胞关系密切（P＜0.05）。结论QKI被鉴定为与胶质瘤诊断和预后相关的抑癌基因，提高QKI表达水平有望成为胶质瘤治疗的有效方案。

Abstract： Objective To explore the expression characteristics of Quaking(QKI) gene in glioma and its correlation with prognosis. Methods The relationship between QKI expression level and WHO grade, age, IDH mutation status and chromosome 1p19q deletion in glioma patients was explored by using Chinese Glioma Genome Atlas and The Cancer Genome Atlas. Then, the difference of overall survival time between glioma patients with high and low expression of QKI was compared. Functional enrichment analysis was used to explore the biological function of QKI. TIMER was used to analyze the relationship between QKI expression and glioma immune infiltrating cells. Results The expression level of QKI was significantly decreased in WHO IV glioma patients(P＜0.001). The expression of QKI was higher in glioma patients with age≤41 years(P＜0.001), IDH mutant(P＜0.001) and 1p19q co-deletion(P＜0.001). The survival time of high QKI expression group was longer than that of low QKI expression group(P＜0.001). Cox regression model analysis showed that high QKI expression was independent factor related to the survival of glioma patients(P=0.038). Bioinformatics analysis showed that the functions of QKI-related expression genes were mainly enriched in biological processes such as RNA splicing, cell granules and protease activation. In the glioma immune microenvironment, QKI is closely related to a variety of immune infiltrating cells(P<0.05). Conclusion QKI is identified as a tumor suppressor gene associated with the diagnosis and prognosis of glioma and is expected to become a therapeutic target for glioma.