摘要
目的探讨胸腺细胞选择相关高迁移率族蛋白(TOX)基因表达与较低级别胶质瘤(LGG)患者放疗敏感性的关系。方法采用生物信息学研究方法,选取肿瘤基因组图谱(TCGA)数据库中的474例LGG患者作为试验集(TCGA-474集),中国脑胶质瘤基因组图谱(CGGA)数据库中的两个不同的遗传数据集(分别包括412例和171例患者)作为验证集(CGGA-412集和CGGA-171集)。根据是否接受放疗将患者分层,根据TOX基因在LGG中的表达水平分为TOX高表达组和低表达组,绘制患者生存曲线,采用log-rank检验对比分析TOX高表达组和低表达组患者的总生存(OS)和无进展生存(PFS)。结果TCGA-474集患者OS多因素分析显示TOX高表达是OS的保护因素(HR=0.061,95%CI为0.005~0.791,P=0.044)。按放疗与否分层并调整混杂因素后,TOX高表达组患者在TCGA-474集、CGGA-412集、CGGA-171集的HR(95%CI)分别为0.405(0.261~0.629)、0.581(0.418~0.806)和0.464(0.269~0.800),P值分别为<0.001、0.001、0.008。TCGA-474集的放疗患者中,TOX高表达组患者的OS(P<0.001)和PFS(P<0.001)均较低表达组延长,差异有统计学意义。TOX高表达组患者的OS获益在CGGA-412集(P<0.001)和CGGA-171集(P<0.001)均较低表达组延长,差异有统计学意义。结论TOX的高表达可能与LGG的放疗敏感性有关,可能是LGG放疗敏感性的一个基因标记。
Objective To investigate the relationship between the expression level of thymocyte selection-associated high mobility group box protein(TOX)gene and the radiosensitivity of lower-grade glioma(LGG)patients.Methods Using bioinformatics research methods,474 LGG patients from The Cancer Genome Atlas(TCGA)database were selected as the test set(TCGA-474 set),and two different genetic data sets(n=412 and n=171)from the Chinese Glioma Genome Atlas(CGGA)database were selected as the validation set(CGGA-412 set and CGGA-171 set).Patients were stratified based on whether received radiotherapy,and divided into the high and low TOX expression group according to the expression level of TOX gene in LGG.Survival curves of all patients were plotted.The overall survival(OS)and progression-free survival(PFS)of patients in the high and low TOX expression groups were compared and analyzed using log-rank test.Results Multivariate analysis of OS in the TCGA-474 set showed that high expression of TOX was a protective factor for OS(HR=0.061,95%CI:0.005-0.791,P=0.044).After stratification analysis based on radiotherapy and adjustment for confounding factors,the HR(95%CI)of patients with high TOX expression in the TCGA-474,CGGA-412,and CGGA-171 sets were 0.405(0.261-0.629),0.581(0.418-0.806),and 0.464(0.269-0.800),respectively,with P values of<0.001,0.001,and 0.008,respectively.Among patients receiving radiotherapy in the TCGA-474 set,the OS and PFS of patients with high TOX expression were significantly longer than those in the low TOX expression group,and the differences were statistically significant(both P<0.001).The OS benefit of patients with high expression of TOX was significantly prolonged in both the CGGA-412 and CGGA-171 sets compared to those with low TOX expression,and the differences were statistically significant(both P<0.001).Conclusion The high expression of TOX may be related to the radiosensitivity of LGG,which may be a gene marker of the radiosensitivity of LGG.
作者
马胤光
孙铭
刘畅
白璐
李慧君
汤在祥
Ma Yinguang;Sun Ming;Liu Chang;Bai Lu;Li Huijun;Tang Zaixiang(Suzhou Medical College of Soochow University,Suzhou 215123,China;Department of Biostatistics,School of Public Health,Suzhou Medical College of Soochow University,Suzhou 215123,China)
出处
《中华放射肿瘤学杂志》
CSCD
北大核心
2023年第9期836-842,共7页
Chinese Journal of Radiation Oncology
基金
国家自然科学基金(81773541)
江苏高校优势学科建设工程资助项目(GZK1201919)。
