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。
Abstract
Objective To investigate the potential value of the cuproptosis gene LIPT1 in the diagnosis and prognosis of glioma. Methods The expression of 10 cuproptosis genes in glioma was mined using TCGA database. The expression of LIPT1 in 18 glioma 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 explore the relationship between LIPT1 and immunological checkpoints, DNA methylation site and DNA mismatch repair genes in gliomas, 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 checkpoint, DNA methylation site and DNA mismatch repair gene (P<0.05). Transcription factors such as FOXG1 were predicted to possibly bind to LIPT1. Drugs such as docetaxel might treat gliomas by targeting and regulating LIPT1-related hub genes. Conclusions LIPT1 may be a potential biomarker and may be associated with poor prognosis of glioma.
关键词
胶质瘤 /
铜死亡基因脂肪酸转移酶-1 /
铜死亡 /
生物标志物
Key words
glioma /
lipoyltransferase 1 /
cuproptosis /
biomarker
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基金
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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