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铜死亡基因LIPT1在脑胶质瘤诊断及预后判断中的价值OACSTPCD

Value of cuproptosis gene LIPT1 in diagnosis and prognosis of brain gliomas

中文摘要英文摘要

目的 探讨铜死亡基因脂肪酸转移酶-1(LIPT1)在胶质瘤诊断及预后判断中的潜在价值.方法 利用TCGA数据库挖掘胶质瘤中 10 种铜死亡基因表达.采用IHC和qRT-PCR 检测 18 例胶质瘤患者中LIPT1 的表达.采用qRT-PCR检测LIPT1 在HEB、U87 和U251 细胞中的表达.采用ROC曲线预测LIPT1 在胶质瘤中的诊断效能.采用Kaplan-Meier生存曲线和Cox分析探索LIPT1 的预后价值.采用ssGSEA数据库评估LIPT1 对胶质瘤免疫浸润的影响.探索胶质瘤中LIPT1 与免疫学检查点、DNA甲基化位点和DNA错配修复基因之间的关系.对LIPT1 相关基因进行GO、KEGG和GSEA功能富集分析.Animal TFDB3 预测LIPT1 相关转录因子.利用GDSC数据库预测针对LIPT1 和hub基因的潜在药物.结果 LIPT1 在胶质瘤中的表达高于正常组织(3.03 vs.2.28,P<0.05).Ⅱ、Ⅲ、Ⅳ级胶质瘤的免疫评分存在差异[(1.47±0.51)vs.(4.94±1.25)vs.(9.88±1.65),P<0.05].HEB、U87 和U251 细胞LIPT1 的mRNA水平存在差异[(0.22±0.03)vs.(0.45±0.04)vs.(0.58±0.05),P<0.05].LIPT1 在胶质瘤诊断中的AUC值为 0.87.LIPT1 高表达组较低表达组OS、DSS、PFI缩短,差异有统计学意义(P<0.05).LIPT1 表达与免疫浸润改变及免疫检查点、DNA甲基化位点和DNA错配修复基因的表达存在相关性(P<0.05).FOXG1 等转录因子可能与LIPT1 结合.多西他赛等药物可能通过靶向调控LIPT1 相关hub基因治疗胶质瘤.结论 LIPT1 可能是胶质瘤的潜在生物标志物,与胶质瘤不良预后有关.

Objective To investigate the potential value of the cuproptosis gene LIPT1 in the diagnosis and prognosis of glio-ma.Methods The expression of 10 cuproptosis genes in glioma was mined using TCGA database.The expression of LIPT1 in 18 glio-ma patients was detected by IHC and qRT-PCR.The expression of LIPT1 in HEB,U87 and U251 cells was detected by qRT-PCR.ROC curve was used to predict the diagnostic efficacy of LIPT1 in glioma.Kaplan-Meier survival curve and Cox analysis were used to explore the prognostic value of LIPT1.ssGSEA database was used to evaluate the effect of LIPT1 on immune invasion of glioma.To ex-plore the relationship between LIPT1 and immunological checkpoints,DNA methylation site and DNA mismatch repair genes in glio-mas,fFunctional enrichment of LIPT1-associated genes was performed with GO,KEGG,and GSEA.Animal TFDB3 predicts LIPT1-associated transcription factors.The GSCA database was utilized to predict potential drugs targeting LIPT1 and hub genes.Results LIPT1 expression in glioma was higher than in normal tissues(3.03 vs.2.28,P<0.05).The immune scores of grade Ⅱ,Ⅲ and Ⅳ gliomas were different[(1.47±0.51)vs.(4.94±1.25)vs.(9.88±1.65),P<0.05].The mRNA levels of LIPT1 in HEB,U87 and U251 cells were different[(0.22±0.03)vs.(0.45±0.04)vs.(0.58±0.05),P<0.05].The AUC value of LIPT1 in glioma diagnosis was 0.87.The OS,DSS,and PFI in the high LIPT1 expression group were shorter than those in the low LIPT1 expression group(P<0.05).The LIPT1 expression was correlated with immune infiltration changes and the expression of immune check-point,DNA methylation site and DNA mismatch repair gene(P<0.05).Transcription factors such as FOXG1 were predicted to possi-bly bind to LIPT1.Drugs such as docetaxel might treat gliomas by tar-geting and regulating LIPT1-related hub genes.Conclusions LIPT1 may be a potential biomarker and may be associated with poor prog-nosis of glioma.

林彦琛;徐葳;英草;刘瑞;张玉钰;代二庆;李晶晶

300162 天津,武警特色医学中心康复医学科300162 天津,武警特色医学中心病理科314000,天津中医药大学研究生院300140,天津市第四中心医院药剂科

临床医学

胶质瘤铜死亡基因脂肪酸转移酶-1铜死亡生物标志物

gliomalipoyltransferase 1cuproptosisbiomarker

《武警医学》 2024 (004)

277-285 / 9

天津市教委科研计划项目(2022YGYB07);天津市卫生健康科技项目(TJWJ2022QN100)

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