摘要
目的研究组蛋白H2A变体(H2AX)基因在人肺腺癌中的临床意义,初步探索其在肺腺癌中的生物学作用。方法从癌症基因组图谱和基因表达综合数据库中下载肺腺癌转录组数据,使用R 4.3.1软件提取H2AX mRNA在肺腺癌组织和癌旁正常肺组织中的表达水平,分析H2AX表达与患者临床病理参数之间的关系。使用Kaplan-Meier和Cox回归分析H2AX基因表达对患者的预后作用。使用实时荧光定量PCR(qPCR)验证分析H2AX基因在肺腺癌细胞和正常支气管上皮细胞中的表达。基因集富集分析、基因本体论富集分析和京都基因与基因组百科全书富集分析用于探索H2AX基因的生物学作用。结果与癌旁正常组织比较,H2AX mRNA在肺腺癌组织中表达升高(P<0.001)。qPCR结果显示,与正常支气管上皮细胞相比,肺腺癌细胞A549和SPC-A1中H2AX mRNA表达水平明显升高(P<0.05)。H2AX基因表达与患者的肿瘤分期(P=0.029)和N分期(P=0.016)有关。Kaplan-Meier曲线分析显示,高表达的H2AX与患者总生存率较低有关(P<0.001)。Cox回归分析显示,H2AX是肺腺癌患者的独立预后因素(HR=1.011,95%CI 1.003~1.020,P=0.006)。功能富集分析结果表明,H2AX基因参与了细胞周期、DNA复制、错配修复等分子功能,参与了P53信号通路等与肿瘤发生发展相关的分子通路。结论H2AX基因在人肺腺癌中高表达,与肿瘤患者的恶性进展相关,可以通过多种途径影响肺腺癌的进展,有望成为肺腺癌患者的分子标志物。
Objective To investigate the clinical significance of H2A histone family member(H2AX)gene in human lung adenocarcinoma,and to explore its biological role in lung adenocarcinoma.Methods The transcriptome data of lung adenocarcinoma were downloaded from the Cancer Genome Atlas and Gene Expression database.The expression of H2AX mRNA in lung adenocarcinoma tissues and adjacent normal lung tissues was extracted by R 4.3.1 software,and the relationship between the expression of H2AX and the clinicopathological parameters of the patients was analyzed.Kaplan-Meier and Cox regression analysis were used to analyze the prognostic value of H2AX gene expression.The expression of H2AX gene in lung adenocarcinoma cell lines and normal bronchial epithelial cells was verified by quantitative real-time PCR(qPCR).Gene set enrichment analysis,gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were used to explore the biological role of H2AX gene.Results The expression of H2AX mRNA in lung adenocarcinoma tissues was significantly higher than that in adjacent normal tissues(P<0.001).qPCR results showed that compared with normal bronchial epithelial cells,the expression levels of H2AX mRNA in lung adenocarcinoma cell lines A549 and SPC-A1 were significantly increased(P<0.05).H2AX expression was associated with tumor stage(P=0.029)and N stage(P=0.016).Kaplan-Meier curve analysis showed that high expression of H2AX was associated with a lower overall survival rate of patients(P<0.001).Cox regression analysis showed that H2AX was an independent prognostic factor for lung adenocarcinoma patients(HR=1.011,95%CI 1.003—1.020,P=0.006).The results of functional enrichment analysis showed that H2AX gene was involved in molecular functions such as cell cycle,DNA replication,mismatch repair,and P53 signaling pathway.Conclusion H2AX gene is highly expressed in human lung adenocarcinoma,which is related to the malignant progression of tumor patients.H2AX gene can affect the progression of lung adenocarcinoma through a variety of pathways,and may be used as a molecular marker for lung adenocarcinoma patients.
作者
黄奔
郑弘熙
顾敏
HUANG Ben;ZHENG Hongxi;GU Min(Department of Laboratory Medicine/Branch of National Clinical Research Center for Laboratory Medicine,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210029,China)
出处
《国际检验医学杂志》
2025年第5期535-542,共8页
International Journal of Laboratory Medicine
基金
江苏省医学重点学科项目(ZDXK202239)。
关键词
组蛋白H2A变体基因
肺腺癌
表达
预后标志物
功能富集分析
H2A histone family member gene
lung adenocarcinoma
expression
prognostic markers
functional enrichment analysis
