ARID1A突变对肝细胞癌早期诊断和治疗效果评估的价值研究  

The evaluation of ARID1A mutation in the early diagnosis and therapeutic effect of hepatocellular carcinoma

作　　者：刘敏[1] 黄满仙 万小兵[1] 陈红[1] 伍娟[1] 孙昌理 LIU Min;HUANG Manxian;WAN Xiaobing;CHEN Hong;WU Juan;SUN Changli(Department ofClinicalLaboratory,NanchangHongduHospital of Traditional Chinese Medicine,Jiangxi,Nanchang,330038,China)

机构地区：[1]南昌市洪都中医院检验科,江西南昌330038

出　　处：《实验与检验医学》2024年第5期424-431,458,共9页Experimental and Laboratory Medicine

基　　金：江西省卫生健康委科技计划项目,编号202140172。

摘　　要：目的本研究旨在从肝细胞癌(hepatocellular carcinoma,HCC)高频突变基因(Top30)中筛选与肿瘤突变负荷(tumor mutation burden,TMB)及患者预后相关的突变基因,并评估其在HCC早期诊断与治疗中的潜在应用价值。方法通过分析癌症基因组图谱(the cancer genome atlas,TCGA)和国际肿瘤基因组协会(international cancer genome consortium,ICGC)数据库中HCC相关数据,采用曼-惠特尼秩和检验(Mann-Whitney U检验)对突变型与野生型HCC的TMB进行比较,并利用免疫细胞浸润估计分析工具CIBERSORT(cell-type identification by estimating relative subsets of RNA transcripts)评估免疫细胞的浸润情况。结果研究发现,在19个突变基因中,富含AT的相互作用结构域蛋白1A(AT-rich interactive domain-containing protein 1A,ARID1A)基因突变不仅与TMB显著相关,还可作为HCC预后的独立预测因子。此外,我们构建了结合ARID1A突变状态、肿瘤分期及TMB的生存预测模型。无论是ARID1A野生型还是突变型,其mRNA和蛋白水平均显著升高,并与患者性别及肿瘤分期存在相关性。结论综上所述,ARID1A突变是HCC诊断的重要生物标志物,并可能成为治疗HCC的潜在靶点。Objective This study aims to identify mutation genes associated with tumor mutation burden(TMB)and patient prognosis from the top 30 high-frequency mutated genes in hepatocellular carcinoma(HCC),and to evaluate their potential application value in the early diagnosis and treatment of HCC.Methods By analyzing HCC-related data obtained from The Cancer Genome Atlas(TCGA)and the International Cancer Genome Consortium(ICGC)databases,we compared the TMB between mutated and wild-type HCC using the Mann-Whitney U test.Additionally,we assessed the infiltration of immune cells using the CIBERSORT(Cell-type Identification by Estimating Relative Subsets of RNA Transcripts)tool.Results Nineteen common mutated genes were identified,but only the ARID1A mutation was strongly associated with TMB and prognosis,acting as an independent predictor of HCC.Furthermore,a survival prediction model was developed,integrating ARID1A mutation status,tumor stage,and TMB.Moreover,elevated levels of ARID1A mRNA and protein were observed in HCC patients,irrespective of ARID1A mutation status,and these levels were associated with both gender and tumor stage.Conclusion In conclusion,the ARID1A mutation serves as a significant biomarker for the diagnosis of HCC and may represent a promising target for therapeutic intervention.

关 键 词：富含AT的相互作用结构域蛋白1A 肿瘤突变负荷 预后标志物 免疫浸润 肝细胞癌 

分 类 号：R735.7[医药卫生—肿瘤]