摘要： 目的 探讨长链非编码RNA基因APTR扩增在胶质瘤细胞增殖和侵袭中的作用及其对胶质瘤患者预后评估的潜在价值。方法 采用实时定量聚合酶链反应（qRT-PCR）检测本院共30例WHO Ⅱ~Ⅳ级胶质瘤组织中APTR基因扩增及表达水平，并收集肿瘤基因组学图谱计划（TCGA）数据库中1119例WHOⅡ~Ⅳ级胶质瘤组织中APTR基因扩增及表达数据，分析两组病例APTR基因扩增阳性率与胶质瘤WHO分级、APTR LncRNA表达水平及患者预后的关系，噻唑蓝（MTT）法及Transwell侵袭实验检测APTR基因对胶质瘤细胞增殖活性和侵袭能力的影响。结果 TCGA数据库组APTR基因扩增阳性率与胶质瘤分级呈同步递增且差异有统计学意义（χ2=53.901， P=0.000； χ2=267.832， P=0.000； χ2= 118.412， P=0.000）。Spearman秩相关分析显示，APTR基因拷贝数扩增程度与APTR LncRNA表达水平呈正相关（本院病例组： rs=0.917， P=0.000； TCGA数据库病例组： rs=0.591， P=0.000）。单因素和多因素逐步法Cox回归分析显示，APTR基因扩增及由此引起的APTR LncRNA过表达均是患者预后不良的危险因素（均P<0.05）。敲低胶质瘤细胞APTR基因表达可显著抑制其增殖及侵袭。结论 胶质瘤细胞中 APTR基因扩增及由此引起的APTR LncRNA过表达均可作为评估胶质瘤患者预后的新预测因素，也是促进胶质瘤细胞增殖和侵袭的重要因素。

关键词: 神经胶质瘤, 分子生物学, APTR基因扩增（非MeSH词）

Abstract: Objective To explore the potential effect of long non-coding RNA APTR gene amplification on glioma cell proliferation and invasion and glioma patients' prognosis. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the APTR gene amplification and expression condition of 30 cases of World Health Organization (WHO) grade Ⅱ-Ⅳ glioma patients from Tianjin Medical University General Hospital, and the APTR amplification and expression in 1119 cases of glioma patients from The Cancer Genome Atlas (TCGA) database. The correlation of APTR amplification rate with glioma grade, APTR LncRNA level and patients' prognosis was accessed. The effects of APTR gene on proliferation and invasion in U251 glioma cells were further confirmed by methyl thiazolyl tetrazolium (MTT) assay and Transwell assay. Results The APTR amplification rate was positively correlated with glioma grade,the results were significant (χ2=53.901, P= 0.000; χ2 =267.832, P =0.000; χ2 =118.412, P =0.000). APTR amplification rate was also positively correlated with APTR LncRNA level(patientsfrom ourhospital: rs=0.917, P=0.000;patientsfrom TCGA: rs = 0.591, P = 0.000). Univariate and multivariate stepwise Cox regression results showed APTR amplification and LncRNA level were independent predictors of poorer prognosis of glioma patients(all P< 0.05). Knocking down APTR gene in glioma cells could inhibit cell proliferation and invasion. Conclusions APTR amplification and induced APTR LncRNA over-expression are novel independent glioma prognosis biomarkers,which could provide valuable information for grading and prognosise valuation of glioma patients,and could also become key factor to promote glioma cell proliferation and invasion.

Key words: Glioma, Molecular biology, APTR gene amplification(not in MeSH)