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乙酰辅酶A羧化酶相关树突状细胞标记预测肝癌患者的预后及潜在治疗药物识别
引用本文:闫长孟,韩君. 乙酰辅酶A羧化酶相关树突状细胞标记预测肝癌患者的预后及潜在治疗药物识别[J]. 中国现代医生, 2024, 62(5): 82-86
作者姓名:闫长孟  韩君
作者单位:葫芦岛市中心医院消化内科,辽宁葫芦岛 125000;北京康仁堂药业有限公司中药研究院,北京 101301
摘    要:目的 研究乙酰辅酶A羧化酶(acetyl-coa carboxylase 1,ACACA)基因在肝癌中的表达、预后价值及其与免疫细胞的相关性,构建肝癌预后模型。方法 整合基因型组织表达(genotype-tissue expression,GTEx)数据库和癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据分析ACACA基因在癌症及癌旁组织的表达差异,预后分析。分析ACACA与免疫细胞的相关性。使用GSE156625单细胞转录组测序(single cell RNA seq,scRNA-seq)数据研究ACACA在树突状细胞(dendritic cells,DCs)中的表达。建立基于载脂蛋白C-Ⅰ(apolipoprotein c-Ⅰ,APOC1)和载脂蛋白C-Ⅲ(apolipoprotein c-Ⅲ,APOC3)的肝细胞癌(hepatocellular carcinoma,HCC)预后模型,使用Kaplan-Meier生存曲线和时间依赖性受试者操作特征(receiver operator characteristic,ROC)曲线评估预后能力,并通过分子对接分析中药成分在APOC1和APOC3中的作用。结果 ACACA在多种癌症中表达差异显著,与肝癌预后相关。高表达ACACA降低树突状细胞含量。APOC1和APOC3是主要DCs标记基因,与ACACA表达正相关。基于APOC1和APOC3的原发性HCC预后模型具有中等的敏感性和特异性。使用列线图预测TCGA队列中肝癌患者的1年,3年和5年总生存期(overall survival,OS)的可能性,并通过校准曲线分析证实了其可靠性。Salvianolic acid B、Asiaticoside和Neohesperidin可能对APOC1和APOC3具有作用潜力。结论 ACACA与肝癌预后密切相关,基于APOC1和APOC3的预后模型可作为预测指标,部分中药成分可能对肝癌治疗有潜力。

关 键 词:肝癌;乙酰辅酶A羧化酶;预后;免疫细胞;DCs细胞标记基因

Prediction of prognosis and identification of potential therapeutic agents for liver cancer patients based on acetyl-coa carboxylase 1-associated dendritic cell
Abstract:Objective To investigate the expression, prognostic value of acetyl-coa carboxylase 1 (ACACA) gene in liver cancer, its correlation with immune cells, and to construct a prognostic model. Methods Integrating genotype-tissue expression (GTEx) and the cancer genome atlas (TCGA) data to analyze ACACA expression in cancers and adjacent tissues, and perform prognosis analysis. Examine the correlation between ACACA and immune cells. Use GSE156625 cell RNA seq (scRNA-seq) data to study ACACA expression in dendritic cells (DCs). Construct an hepatocellular carcinoma (HCC) prognosis model based on apolipoprotein c-Ⅰ(APOC1) and apolipoprotein c-Ⅲ (APOC3), using Kaplan-Meier survival curves and time-dependent receiver operator characteristic (ROC) curves to evaluate prognostic capability, and analyze the effect of traditional Chinese medicine components on APOC1 and APOC3 through molecular docking. Results ACACA shows significant differential expression in various cancers and is associated with the prognosis of liver cancer. High expression of ACACA reduces the content of dendritic cells. APOC1 and APOC3, the major DCs marker genes, were positively correlated with ACACA expression. Using Kaplan-Meier curves, we predicted the 1-year, 3-year, and 5-year overall survival (OS) probabilities for HCC patients in the TCGA cohort, and confirmed the reliability through calibration curve analysis. Salvianolic acid B, Asiaticoside, and Neohesperidin may have potential effects on APOC1 and APOC3. Conclusion ACACA is closely related to HCC prognosis, and the prognostic model based on APOC1 and APOC3 can serve as a predictive indicator. Some traditional Chinese medicine components may hold therapeutic potential for HCC treatment.
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