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中华肺部疾病杂志(电子版) ›› 2024, Vol. 17 ›› Issue (06) : 888 -894. doi: 10.3877/cma.j.issn.1674-6902.2024.06.007

论著

基于TCGA 数据库肺腺癌铁死亡相关基因CA9 的鉴定
汪艳1,2, 孙美玲3,(), 闵凌峰3,()   
  1. 1.225009 扬州,扬州大学医学院
    2.211700 淮安,盱眙县人民医院呼吸与危重症医学科
    3.225001 扬州,扬州大学附属苏北人民医院呼吸与危重症医学科
  • 收稿日期:2024-08-13 出版日期:2024-12-25
  • 通信作者: 孙美玲, 闵凌峰
  • 基金资助:
    国家自然科学基金资助项目(81870033)

Identification of CA9,an iron death-related gene in lung adenocarcinoma based on the TCGA database

Yan Wang1,2, Meiling Sun3,(), Lingfeng Min,3()   

  1. 1.Medical college,Yangzhou Universtity, Yangzhou 225009,China
    2.Department of Respiratory and Critical Care Medicine, Xuyi People's Hospital,Huaian 211700, China
    3.Department of Respiratory and Critical Care Medicine, Northern Jiangsu People' s Hospital, Yangzhou Universtity, Yangzhou 225001, China
  • Received:2024-08-13 Published:2024-12-25
  • Corresponding author: Meiling Sun, Lingfeng Min
引用本文:

汪艳, 孙美玲, 闵凌峰. 基于TCGA 数据库肺腺癌铁死亡相关基因CA9 的鉴定[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(06): 888-894.

Yan Wang, Meiling Sun, Lingfeng Min. Identification of CA9,an iron death-related gene in lung adenocarcinoma based on the TCGA database[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2024, 17(06): 888-894.

目的

分析并验证影响肺腺癌(lung adenocarcinoma,LUAD) 预后的关键铁死亡(ferroptosis)相关基因及药物敏感性。

方法

从癌症基因组图谱数据库(The cancer genome atlas,TCGA)、基因表达数据库(gene expression omnibus,GEO)数据库下载数据。 对数据库中下载的转录组表达谱进行差异表达分析、基因本体数据库(gene ontology,GO)和京都的基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGC)富集分析、加权基因共表达网络分析(weighted gene coexpression network analysis,WGCNA)共表达分析,与铁死亡相关基因取交集并进行乘积极限法(Kaplan-Meier,KM)生存分析,获得关键基因,进行药物敏感性分析。

结果

TCGA 数据集中,LUAD 样本和正常样本中共筛选964 个差异表达基因(differentially expressed genes,DEGs),其中259 个表达上调,705 个表达下调。 GSE46539 数据集中有193 个DEGs,其中108 个上调,85 个下调。 964 个DEGs 进行GO 功能富集分析和KEGG 通路富集分析显示,DEGs 主要参与的生物学功能为细胞外基质组织、细胞外结构组织、外部封装结构组织、细胞黏附的正向调节、伤口愈合、含胶原蛋白的细胞外基质、胶原蛋白三聚体、薄膜筏膜微域、内细胞囊泡、细胞外基质结构成分、糖胺聚糖结合、肝素结合、整合素结合、细胞因子结合。WGCNA 共表达分析分别获得5303,362 个基因。 将TCGA 和GSE46539 数据集的DEGs、WGCNA 与FRGs 取交集,确定2 个重叠基因配对(couple,CP)和碳酸酐酶9(carbonic anhydrase 9,CA9)。 与正常样本相比,CP 和CA9 高表达于LUAD 样本(P<0.001),两者在泛癌中多数为高表达。 KM 生存分析显示,CA9 高表达者生存期短(P<0.05),CP 对LUAD 生存期的分析差异无统计学意义(P>0.05),CA9 是LUAD 的危险基因,与2 种药物敏感性正相关。

结论

生物信息学验证了影响LUAD 预后的关键铁死亡相关基因CA9,为LUAD 提供了潜在治疗靶点。

Objective

To explore and verify the key Ferroptosis related genes and drug sensitivity analysis that affect the prognosis of lung adenocarcinoma (LUAD).

Methods

Firstly,data were downloaded from TCGA and GEO databases.Secondly,the transcriptome expression profiles downloaded from the databases were subjected to differential expression analysis,GO and KEGG enrichment analysis,WGCNA co-expression analysis,intersection with iron death related genes were taken and KM survival analysis was performed to obtain key genes,and drug sensitivity analysis was performed.

Results

964 (259 upregulated and were downregulated)and 193 differentially expressed genes(108 upregulated and 85 downregulated) were obtained from TCGA dataset and GEO dataset respectively,which were related to extracellular matrix organization and cell adhesion molecule.5 303,362 genes were obtained by WGCNA co-expression analysis,which were intersected with Ferroptosis related genes,and two characteristic genes CP and CA9 were obtained.Compared with normal samples,CP and CA9 were highly expressed in LUAD samples (P<0.001),which were mostly highly expressed in pancarcinoma.KM survival analysis showed that those with high expression of CA9 had a short survival period (P<0.05),while there was no statistically significant difference between CP analysis and LUAD survival period (P>0.05).CA9 was a risk gene of LUAD and positively correlated with the sensitivity of the two drugs.

Conclusions

The key Ferroptosis related gene CA9 which affects the prognosis of lung adenocarcinoma was explored and verified by bioinformatics,which provides a potential therapeutic target for lung adenocarcinoma.

图1 TCGA 数据集和GEO 数据集差异表达基因的鉴定。 注:A、B:来自TCGA 数据集的DEGs 的火山图,红色是上调基因,绿色是下调基因。 C、D:来自GEO 数据集的DEGs 热图,红色是上调基因,绿色是下调基因
图2 GO 和KEGG 富集分析
图3 TCGA 和GEO 数据集与样本性状的相关性
图4 CP 和CA9 在泛癌中表达情况。 注:A:CA9 泛癌表达;B:CP 泛癌表达。 (*表示P<0.05,**表示P<0.005,***表示P<0.0001)
图5 CP 和CA9 的生存分析。 注:A、B:R 包绘制;C、D:GEPIA 数据库绘制
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