ARID1A对肝癌患者预后和中性粒细胞浸润影响的分析及验证  

Analysis and validation of the impact of ARID1A on prognosis and neutrophil infiltration in patients with hepato cellular carcinoma

作　　者：王梦成 孟涛 蔚应飞 童钟 Wang Mengcheng;Meng Tao;Wei Yingfei;Tong Zhong(Department of Hepatobiliary and Pancreatic Surgery,Hefei First People's Hospital,Hefei 230011)

机构地区：[1]安徽医科大学第三附属医院、合肥市第一人民医院肝胆胰外科,安徽合肥230011

出　　处：《中国现代医药杂志》2025年第4期21-29,共9页Modern Medicine Journal of China

摘　　要：目的 在肝癌组织中寻找与中性粒细胞浸润相关的分子,并探究其在肿瘤治疗和评估中的作用。方法 从既往文献中筛选出中性粒细胞的标志基因。基于这些基因,使用R软件包“ConsensusClusterPlus”将肝癌患者划分为不同的亚型。通过单样本基因集富集分析(ssGSEA)和基因集富集分析(GSEA)探究不同亚型间的生物学差异。使用“Limma”包鉴定不同亚型间的差异表达基因。利用GPSAdb网站鉴定与亚型具有相似特征的分子靶点,并通过TIMER及MCPcounter算法分析其对肝癌组织中中性粒细胞浸润程度的影响。通过免疫组织化学染色法检测癌症组织和癌旁组织中AT丰富结合域1A (AT-rich interaction domain 1A,ARID1A)的表达水平及中性粒细胞浸润水平,并分析其与患者临床病理参数的关系。最后,结合TCGA和GEO数据库探究该分子与肝癌患者预后和索拉非尼治疗敏感性的关系。结果 基于10个中性粒细胞标志基因,将肝癌患者分为两个亚型。两个亚型的肝癌患者预后存在显著差异。中性粒细胞标志基因主要与白细胞迁移及细胞免疫等细胞功能相关。GPSAdb网站识别出ARID1A与肝癌的中性粒细胞亚型具有相似特征。免疫组化实验结果表明,与癌旁组织相比,肝癌细胞中ARID1A的表达水平显著升高,且ARID1A高表达的组织中,中性粒细胞浸润水平也显著升高。TIMER及MCPcounter算法分析表明,ARID1A促进肝癌中中性粒细胞的浸润,并预测肝癌患者的不良预后和对索拉非尼治疗的耐药性。结论 ARID1A是预测肝癌患者预后的一个生物标志物,并促进肝癌中中性粒细胞浸润和索拉非尼耐药。Objective To identify molecules associated with neutrophil infiltration in hepatocellular carcinoma(HCC)and investigate their roles in tumor therapy and prognosis assessment.Methods Neutrophil marker genes were identified from previous literature.Using the R package"ConsensusClusterPlus",HCC patients were classified into subtypes based on these genes.Single-sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were employed to explore biological differences between subtypes.Differentially expressed genes between subtypes were identified using the"Limma"package.The GPSAdb website was utilized to identify molecular targets with similar characteristics to the subtypes,and TIMER and MCPcounter algorithms were used to analyze their impact on neutrophil infiltration in HCC tissues.Immunohistochemistry(IHC)staining was performed to detect ARID1A(AT-Rich Interaction Domain 1A)expression levels and neutrophil infiltration in cancerous and adjacent tissues,and their correlation with clinical and pathological parameters was analyzed.Finally,the relationship between ARID1A and patient prognosis,as well as sensitivity to sorafenib treatment,was investigated using data from the TCGA and GEO databases.Results Ten neutrophil marker genes divided HCC patients into two subtypes with significantly different prognoses.These marker genes were primarily associated with cellular functions such as leukocyte migration and cellular immunity.The GPSAdb website identified ARID1A as a molecule with similar characteristics to the neutrophil subtype in HCC.IHC results demonstrated that ARID1A expression in HCC cells was significantly increased compared to adjacent tissues,and tissues with high ARID1A expression exhibited elevated neutrophil infiltration.TIMER and MCPcounter analyses indicated that ARID1A promoted neutrophil infiltration in HCC and predicts poor prognosis and sorafenib resistance in patients.Conclusion ARID1A serves as a biomarker for predicting HCC prognosis and contributes to neutrophil infiltration

关 键 词：ARID1A 肝癌 中性粒细胞 免疫浸润 

分 类 号：R735.7[医药卫生—肿瘤]