ABCC3蛋白在脑胶质瘤中的表达及临床意义

Expression and clinical significance of ABCC3 in gliomas

目的分析ATP结合盒转运蛋白3（ABCC3）在脑胶质瘤患者中的表达情况和临床意义，并探讨该蛋白在脑胶质瘤中可能参与的生物学过程。方法回顾性分析中国脑胶质瘤基因组图谱计划（CGGA）mRNA芯片数据库中309例脑胶质瘤患者的临床资料及mRNA芯片数据，分析ABCC3蛋白的表达特征。同时以TCGARNA测序数据库、GSEl6011mRNA芯片数据库及REMBRANDTmRNA芯片数据库中的胶质瘤数据作为对照，对ABCC3蛋白的表达特征进行验证。利用Kaplan—Meier生存曲线和Cox回归分析评价ABCC3蛋白对胶质瘤患者预后的作用。通过基因本体分析获得ABCC3蛋白相关基因的功能和可能参与的信号通路。结果ABCC3的表达量随着病理级别逐渐升高[WHOⅡ-Ⅳ级ABCC3的表达量分别为0．232（0．481）、0．655（1．420）和2．260（2．965），均P〈0．01]；ABCC3在恶性程度较高的间质型、异柠檬酸脱氢酶1（IDHl）野生型和O6-甲基鸟嘌呤DNA甲基转移酶（MGMT）野生型脑胶质瘤中的表达水平更高[分别为3．518（1．988）、2．366（3．020）和1．864（3．036），均P〈0．01]。在胶质母细胞瘤和低级别胶质瘤中ABCC3蛋白高表达组患者的累积生存率明显低于低表达组（P〈0．05）。多因素分析结果显示，病理级别、Karnofsky功能状态评分（KPS）、放疗和ABCC3蛋白的表达量是影响胶质瘤患者生存期的独立因素（P〈0．05），可用于预后判断。结论ABCC3蛋白可能与胶质瘤细胞的细胞黏附、炎症应答、低氧应答、血管生成和趋药性等生物学过程有关；ABCC3蛋白可能参与胶质瘤肿瘤坏死因子信号通路、P13K—AKT和JAK—STAT等信号通路。ABCC3蛋白可促进脑胶质瘤进展，可作为患者预后判断的指标及潜在的治疗靶点。

Objective To analyze the expression and clinical features of ATP binding cassette subfamily C member 3 （ABCC3） in gliomas and to investigate the biological processes and signal pathway involved in glioma cells by ABCC3. Methods The clinical data and expression information of ABCC3 in 309 glioma patients were collected retrospectively from the CGGA mRNA sequencing data of China. TCGA mRNA sequencing, GSE16011 mRNA micro array datasets and REMBRANDT mRNA datasets were used as validation sets. Kaplan-Meier method and Cox regression analysis were used to investigate the role of ABCC3 in the prognosis of patients. Gene ontology （go） analysis was used to obtain biological processes involved in ABCC3 expression. KEGG pathway analysis was performed to study the signal pathway related to the expression of ABCC3. Results The expression of ABCC3 in high-grade gliomas was significantly higher than that in low-grade gliomas [0. 232 （0. 481 ）, 0. 655 （ 1. 420） and 2. 260 （2. 965 ） respectively from WHO Ⅱ to Ⅳ, all P 〈 0. 01 ]. The expression of ABCC3 was higher in malignant molecular subtype mesenchymal, IDH1 wild-type and MGMT wild-type gliomas [3. 518 （1. 988）, 2. 366 （3. 020） and 1. 864 （ 3. 036）, respectively, all P 〈 0. 01 ]. The cumulative survival rate of patients with high expression of ABCC3 was significantly lower than that of patients with low expression in both LGG and GBM （ P 〈 0. 05 ）. Moreover, multivariate analysis showed that ABCC3 was an independent marker of glioma in glioma patients （P 〈 0. 05）. Conclusions ABCC3 may be associated with the biological process of glioma such as cell adhesion, inflammatory reaction, hypoxia response, angiogenesis and chemotaxis. ABCC3 has been found to be related to tumor necrosis factor signal pathway, PI3K-AKT and JAK-STAT signal pathway. ABCC3 could promote the development of glioma and thus be used as a prognostic indicator and potential therapeutic target.