ADAMTS7基因表达水平对神经胶质瘤患者预后作用及临床病理特征的关联性探讨

The relationship between ADAMTS7 gene expression level and prognostic effect and clinicopathologic characteristics of glioma patients

目的探讨血小板反应蛋白提取整合素金属肽酶7(ADAMTS7)基因表达水平对神经胶质瘤患者预后作用及临床病理特征的关联性。方法在中国胶质瘤基因组图谱(CGGA)数据库(http://www.cgga.org.cn)下载mRNAseq 693和mRNAseq 325两个转录组测序数据集,以mRNAseq 693作为探索数据集,mRNAseq 325作为验证数据集。提取数据集病例的ADAMTS7基因表达量,以ADAMTS7的中位值作为截断阈值将患者分为高表达组和低表达组。分析ADAMTS7基因表达水平与患者临床病理特征的关联性及对患者生存预后的影响,并以美国癌症基因组图谱数据库(TCGA)胶质瘤队列作为外部数据集再次验证ADAMTS7基因表达水平与胶质瘤患者预后的关系。结果无论是在探索数据集还是在验证数据集中,ADAMTS7基因高表达组与低表达组在发生状态、组织学类型、WHO分级、化疗状态、异柠檬酸脱氢酶(IDH)突变状态和1号染色体短臂和19号染色体长臂(1p19q)共缺失状态方面比较差异均有统计学意义(P<0.05)。对于探索数据集,多因素Cox回归分析结果显示,较高的ADAMTS7基因表达水平、疾病复发、WHO分级为Ⅳ级和年龄>43岁是影响患者术后生存预后的危险因素,而接受化疗、IDH突变和1p19q共缺失是影响患者术后生存预后的保护因素(P<0.05)。对于验证数据集,多因素Cox回归分析结果显示,较高的ADAMTS7基因表达水平、疾病复发、WHO分级为Ⅳ级是影响患者术后生存预后的危险因素,而组织学类型为多形胶质母细胞瘤(GBM)、接受化疗和1p19q共缺失是影响患者术后生存预后的保护因素(P<0.05)。Kaplan-Meier生存分析结果显示,无论是对于探索数据集还是验证数据集,ADAMTS7基因低表达组的术后生存预后均显著优于高表达组(P<0.001)。以TCGA胶质瘤数据作为外部数据集验证,结果显示,ADAMTS7基因高表达组的总生存期(OS)和无进展间期(PFI)优于低表达组,差异有统计学意义(P<0.001)。结论ADAMTS7基因表达水平可作为评估神经胶质瘤患者预后的预测因子,具有潜在的临床应用价值。

Objective To explore the relationship between a disintegrin and metalloproteinase with thrombospondin motifs 7(ADAMTS7)gene expression level and the prognosis and clinical characteristics of glioma patients.Methods Two transcriptome sequencing data sets,mRNAseq 693 and mRNAseq 325,were downloaded from Chinese Glioma Genome Atlas(CGGA)Database(http://www.cgga.org.cn).The mRNAseq 693 was used as an exploration data set,and the mRNAseq 325 as a validation data set.The ADAMTS7 gene expressions of the data set cases were extracted,and the median value of ADAMTS7 was used as the cutoff threshold to divide the patients into high expression group and low expression group.The relationship between ADAMTS7 gene expression level and the clinicopathological characteristics of the patients and its impact on the patients′survival prognosis were analyzed.The Cancer Genome Atlas(TCGA)glioma cohort was used as an external data set to verify the relationship between ADAMTS7 gene expression level and the prognosis of glioma patients.Results Whether in the exploration data set or in the validation data set,the differences between the ADAMTS7 gene high expression group and the low expression group were statistically significant in terms of occurrence status,histological type,World Health Organization(WHO)classification,chemotherapy status,isocitrate dehydrogenase(IDH)mutation status,and chromosome 1 short arm and chromosome 19 long arm(1p19q)co-deletion status(P<0.05).For the exploration data set,the results of multivariate Cox regression analysis showed that higher level of ADAMTS7 gene expression,disease recurrence,WHO gradeⅣand age>43 years were the risk factors for survival prognosis of the patients,while receiving chemotherapy,IDH mutation and 1p19q co-deletion were the protective factors for postoperative prognosis of the patients(P<0.05).For the validation data set,the results of multivariate Cox regression analysis showed that higher ADAMTS7 gene expression level,disease recurrence,and WHO classification of gradeⅣwere the risk factors for survival prognosis of the patients,while the histological type of glioblastoma(GBM),receiving chemotherapy and 1p19q co-deletion were the protective factors for the patients′postoperative survival prognosis(P<0.05).The results of Kaplan-Meier survival analysis showed that,whether in the exploration data set or in the validation data set,the survival prognosis of the ADAMTS7 gene low expression group was significantly better than that of the high expression group(P<0.001).Using TCGA glioma data as an external data set,the results showed that the overall survival(OS)and progression-free interval(PFI)of the ADAMTS7 gene high expression group were better than those of the low expression group,and the differences were statistically significant(P<0.001).Conclusion ADAMTS7 gene expression level can be used as a predictor for evaluating the prognosis of glioma patients,and has potential clinical application value.