空军军医大学学报2024,Vol.45Issue(6) :678-685.DOI:10.13276/j.issn.2097-1656.2024.06.014

基于泛素化相关长链非编码RNA构建胶质母细胞瘤患者预后风险评估模型

Construction of prognostic risk assessment model of glioblastomas based on ubiquitination-related long non-coding RNAs

李晓宾 宿长军 杨倩
空军军医大学学报2024,Vol.45Issue(6) :678-685.DOI:10.13276/j.issn.2097-1656.2024.06.014

基于泛素化相关长链非编码RNA构建胶质母细胞瘤患者预后风险评估模型

Construction of prognostic risk assessment model of glioblastomas based on ubiquitination-related long non-coding RNAs

李晓宾 1宿长军 2杨倩3
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作者信息

  • 1. 空军军医大学唐都医院实验外科,陕西西安 710038;空军军医大学唐都医院神经内科,陕西西安 710038
  • 2. 空军军医大学唐都医院神经内科,陕西西安 710038
  • 3. 空军军医大学唐都医院实验外科,陕西西安 710038
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摘要

目的 采用生物信息学方法,运用两个数据库筛选胶质母细胞瘤(GBM)患者差异表达的泛素化相关长链非编码RNA(lncRNA)并构建预后风险评估模型.方法 从癌症基因组图谱数据库和中国脑胶质瘤基因组图谱计划数据库下载GBM患者测序数据和对应的临床数据.应用Pearson相关分析筛选出两个数据库共有的泛素化相关lncRNA.进一步运用单因素Cox回归分析和最小绝对收缩和选择算子回归分析筛选与生存显著相关的泛素化相关lncRNA并构建预后模型;对模型预测的有效性进行内部队列和外部队列验证,并对模型高、低风险组进行生存分析、基因功能富集分析、免疫微环境分析以及药物反应预测.结果 两个数据库筛选出共有的泛素化相关lncRNA 409个,经过严格筛选,最终分析出9个与GBM预后显著相关的关键泛素化相关lncRNA,并构建预后风险评分模型.所有患者依据预后风险评分被分为高、低风险组.生存曲线显示,在训练队列、测试队列以及外部队列中高风险组总生存期均显著低于低风险组(P<0.05);受试者工作特征曲线显示,该模型对患者1、3、5年的总生存期具有较好的预测价值(P<0.05);风险模型中高风险和低风险组的免疫相关通路以及免疫微环境有明显差异,且高风险组患者对药物治疗的应答水平更低(P<0.05).结论 本文利用公共数据库成功构建GBM泛素化相关lncRNA的预后风险评估模型.随后通过不同队列进行效能验证,结果显示该模型对GBM预后情况均有较好的预测价值,且可能与免疫微环境密切相关.这有助于确定GBM患者的预后生物标志物并对未来治疗GBM提供新的思路.

Abstract

Objective To screen the differentially expressed ubiquitination-related long non-coding RNAs(lncRNAs)in glioblastoma(GBM)patients by bioinformatics methods based on two databases and to construct a prognostic risk assessment model.Methods The sequencing data and corresponding clinical data of GBM patients were downloaded from The Cancer Genome Atlas database and Chinese Glioma Genome Atlas database.The ubiquitination-related lncRNAs shared between the two databases were screened by Pearson correlation analysis.Furthermore,univariate Cox regression analysis and least absolute shrinkage and selection operator regression analysis were used to screen ubiquitination-related lncRNAs associated with survival and construct prognostic models.The validity of the model prediction was verified in an internal cohort and an external cohort,and survival analysis,gene function enrichment analysis,immune microenvironment analysis and drug response prediction were performed in the high-risk and low-risk groups of the model.Results A total of 409 shared ubiquitination-related lncRNAs were screened from the two databases.After rigorous screening,nine key ubiquitination-related lncRNAs significantly associated with GBM prognosis were finally analyzed,and a prognostic risk scoring model was constructed.All patients were divided into high-risk group and low-risk group on the basis of the prognostic risk score.The survival curve revealed that the overall survival of the high-risk group was significantly lower than that of the low-risk group in the training cohort,test cohort and external cohort(P<0.05).Receiver operating characteristic curve revealed that the model had a good predictive value for 1-,3-and 5-year overall survival(P<0.05).In the risk model,there were significant differences in immune-related pathways and immune microenvironment between high-risk group and low-risk group,and the response level of patients in high-risk group to drug therapy was lower(P<0.05).Conclusion In this paper,a prognostic risk assessment model of ubiquitination-related lncRNAs for patients with GBM is successfully constructed using public databases.Then,the efficacy is verified by different cohorts,and the results show that the model has good predictive value for GBM prognosis and may be closely related to immune microenvironment.This model may help to determine the prognostic biomarkers for GBM patients and provide new ideas for future treatment of GBM.

关键词

胶质母细胞瘤/泛素化/长链非编码RNA/预后模型/免疫微环境

Key words

glioblastomas/ubiquitination/long non-coding RNA/prognostic model/immune microenvironment

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基金项目

国家自然科学基金(31930048)

国家自然科学基金(82221001)

陕西省重点研发计划(2023-ZDLSF-52)

空军军医大学唐都医院"揭榜挂帅"重大科研项目(2022TDGS006)

出版年

2024
空军军医大学学报
第四军医大学

空军军医大学学报

CHSSCD
影响因子:0.372
ISSN:2097-1656
参考文献量2
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