低氧相关生物标志物预测胶质母细胞瘤患者预后的研究  

Prediction of prognosis of patients with glioblastoma by hypoxia related biomarkers

作　　者：梁鑫[1] 陈荣举 付强[2] LIANG Xin;CHEN Rong-ju;FU Qiang(Department of Neurosurgery,the First People's Hospital of Shenyang,Shenyang 110042;Department of Neurosurgery,Shengjing Hospital of China Medical University,Shenyang 110004,China)

机构地区：[1]沈阳市第一人民医院神经外科,辽宁沈阳110042 [2]中国医科大学附属盛京医院神经外科,辽宁沈阳110004

出　　处：《解剖科学进展》2021年第6期669-672,共4页Progress of Anatomical Sciences

基　　金：辽宁省自然科学基金(2019-MS-370)。

摘　　要：目的挖掘低氧相关生物标志物以准确地预测胶质母细胞瘤患者的总体生存期,寻找新的治疗靶点改善患者预后。方法 MTT方法检测细胞增殖;基于癌症基因组图谱(The Cancer Genome Atlas,TCGA)的胶质母细胞瘤患者表达数据构建低氧相关生物标志物;Kaplan-Meier生存曲线分析与患者预后的关系;ROC曲线对标志物预测价值进行评价。结果 MTT实验结果表明,与常氧培养比较,胶质瘤细胞低氧培养后增殖水平增加(P<0.05)。利用单因素、多因素分析,成功构建一个由4个低氧相关基因(DKK3、DUSP6、SPAG4和VEGFC)构成的胶质母细胞瘤预后标志物。Kaplan-Meier生存分析表明,这一标志物与胶质母细胞瘤患者的较短生存期显著相关。以临床病例参数为协变量,Cox单因素、多因素分析结果提示,低氧相关预后标志物为胶质母细胞瘤患者总体生存期的独立预后因素;ROC曲线分析表明,这一低氧相关预后标志物具有较强的预测胶质母细胞瘤患者总体生存期的潜能。结论成功构建与胶质母细胞瘤及预后高度相关的低氧相关生物标志物,有助于进一步了解胶质母细胞瘤的分子基础,指导临床胶质母细胞瘤患者个性化合理用药和开发新的治疗靶点。Objective To mine hypoxia-related biomarkers to accurately predict the overall survival of patients with glioblastoma, and to find new therapeutic targets to improve the prognosis of patients. Methods Hypoxis-related biomarkers were constructed based on the expression data of glioblastoma patients from The Cancer Genome Atlas(TCGA).Kaplan-Meier survival curve was used to analyse the relationship between the biomarkers and prognosis of patients. ROC curve was used to evaluate the predictive value of markers. MTT assay was used to detect cell proliferation. Results MTT assay showed that the proliferation level of glioma cells in hypoxic culture was increased compared with that in normoxic culture(P<0.05). Using univariate and multivariate Cox analysis, a prognostic biomarker of glioblastoma composed of 4 hypoxia-related genes(DKK3, DUSP6, SPAG4 and VEGFC) was successfully constructed. Kaplan-Meier survival analysis showed that this marker was significantly related to the shorter survival time of patients with glioblastoma. With clinical case parameters as covariates, univariate and multivariate Cox analysis results suggested that hypoxia-related prognostic markers were independent prognostic factors for the overall survival of patients with glioblastoma. ROC curves showed that this hypoxia-related prognostic marker had a strong potential to predict the overall survival of patients with glioblastoma. In vitro cell experiments showed that the proliferation of glioma cells increased after hypoxic culture compared with normoxic culture(P<0.05). Conclusion The construction of hypoxia-related biomarkers that are highly related to glioblastoma and prognosis, which will help to further understand the molecular basis of glioblastoma and guide clinical patients with glioblastoma in the personalized and rational use of drugs and develop new therapeutic targets.

关 键 词：胶质母细胞瘤 低氧 总体生存期 预后标志物 

分 类 号：R739.41[医药卫生—肿瘤]