目的基于公共数据库探究亚洲人群肝细胞癌(hepatocellular carcinoma,HCC)与细胞自噬的特征关系。方法从PubMed上文献检索收集232个自噬相关基因(autuphagy-related genes,ARGs)。从癌症基因组图谱(The Cancer Genome Atlas,TCGA)和国...目的基于公共数据库探究亚洲人群肝细胞癌(hepatocellular carcinoma,HCC)与细胞自噬的特征关系。方法从PubMed上文献检索收集232个自噬相关基因(autuphagy-related genes,ARGs)。从癌症基因组图谱(The Cancer Genome Atlas,TCGA)和国际癌症基因组联盟(International Cancer Genome Consortium,ICGC)数据库分别纳入148例亚洲人种HCC样本(TCGA队列)和228例HCC样本(ICGC队列)。采用Kaplan-Meier法在TCGA队列中分析得到24个对HCC患者具有预后价值的ARGs。对TCGA队列采用聚类分析鉴定ARGs分子亚型。对TCGA队列应用LASSO-Cox回归方法建立基于ARGs的风险评分模型,采用ICGC队列作验证。采用单因素和多因素Cox回归分析筛选出具有统计学意义(P<0.01)的指标,用以构建包含ARGs风险评分和临床因素的列线图预测HCC患者的生存预后。采用受试者工作特征(receiver operating characteristic,ROC)曲线评估分析列线图的预测性能。分别采用WebGestalt数据库、TIMER数据库和相应R语言包在ARGs风险评分亚组中分析免疫浸润、富集途径和基因组改变状态。结果基于ARGs的HCC分子亚型[聚类A(Cluster-A)和聚类B(Cluster-B)]患者的总生存期比较,差异具有统计学意义(P<0.01)。使用LASSO-Cox回归方法筛选出特征性的5个预后相关ARGs[5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase(ATIC)、eukaryotic translation initiation factor 2 subunit alpha(EIF2S1)、histone deacetylase 1(HDAC1)、Rac family small GTPase 1(RAC1)和autophagy related 3(ATG3)]构建的风险评分模型将TCGA队列患者分为高风险组和低风险组。两组HCC患者总生存期比较,差异具有统计学意义(P<0.01)。单因素和多因素Cox分析显示,ARGs风险评分和TNM肿瘤分期与HCC患者总生存期相关(均P<0.01)。纳入ARGs风险评分和TNM肿瘤分期的列线图用于预测HCC患者1、3和5年总生存状态具有优秀的预测能力。免疫浸润分析显示,与低风险组比较,高风险组在多数固有免疫细胞和适应免疫细胞浸润水平更高(均P<0.05)。基因本体论(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析显示,高风险组上调基因主要富集于白细胞迁移、细胞运动和分化等多种通路和途径(均P<0.05)。基因组改变差异分析显示,高风险组患者tumor protein p53(TP53)突变频率更高(P=0.003),低风险组患者lysine methyltransferase 2D(KMT2D)突变率更高(P=0.031)。结论本研究建立并验证了基于ARGs的风险评分模型,为预测亚洲人种HCC患者的预后状态提供了一项有效的参考指标。展开更多
The author divided the Baimiao crania into crania Ⅰand crania Ⅱ. According to the comparative result, the author thought the main physical features of crania Ⅰbelonged to the Eastern Asiatic Mongoloid,Crania Ⅱ bel...The author divided the Baimiao crania into crania Ⅰand crania Ⅱ. According to the comparative result, the author thought the main physical features of crania Ⅰbelonged to the Eastern Asiatic Mongoloid,Crania Ⅱ belongs to the Northern Asi atic Mongoloid. The main physical features of crania Ⅰ are mostly similar to those of modern people in northe China. Crania Ⅱ is mostly similar th the modern Mon golian, modern people of north and south China are followed. The main physical fea tures of crania Ⅰ are mostly similar to those of the Xiajiadian upper layer culture,crania Ⅱ is similar to the crania A of Maoqinggou-Yinniugon and Guoxianyaozi cra nia. The author thought the population lived in it should belong to the "Dai"nation which existed during the Spring Autumnand Waring States Period, its nationality may be belong to the ancientn"Di"展开更多
文摘目的基于公共数据库探究亚洲人群肝细胞癌(hepatocellular carcinoma,HCC)与细胞自噬的特征关系。方法从PubMed上文献检索收集232个自噬相关基因(autuphagy-related genes,ARGs)。从癌症基因组图谱(The Cancer Genome Atlas,TCGA)和国际癌症基因组联盟(International Cancer Genome Consortium,ICGC)数据库分别纳入148例亚洲人种HCC样本(TCGA队列)和228例HCC样本(ICGC队列)。采用Kaplan-Meier法在TCGA队列中分析得到24个对HCC患者具有预后价值的ARGs。对TCGA队列采用聚类分析鉴定ARGs分子亚型。对TCGA队列应用LASSO-Cox回归方法建立基于ARGs的风险评分模型,采用ICGC队列作验证。采用单因素和多因素Cox回归分析筛选出具有统计学意义(P<0.01)的指标,用以构建包含ARGs风险评分和临床因素的列线图预测HCC患者的生存预后。采用受试者工作特征(receiver operating characteristic,ROC)曲线评估分析列线图的预测性能。分别采用WebGestalt数据库、TIMER数据库和相应R语言包在ARGs风险评分亚组中分析免疫浸润、富集途径和基因组改变状态。结果基于ARGs的HCC分子亚型[聚类A(Cluster-A)和聚类B(Cluster-B)]患者的总生存期比较,差异具有统计学意义(P<0.01)。使用LASSO-Cox回归方法筛选出特征性的5个预后相关ARGs[5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase(ATIC)、eukaryotic translation initiation factor 2 subunit alpha(EIF2S1)、histone deacetylase 1(HDAC1)、Rac family small GTPase 1(RAC1)和autophagy related 3(ATG3)]构建的风险评分模型将TCGA队列患者分为高风险组和低风险组。两组HCC患者总生存期比较,差异具有统计学意义(P<0.01)。单因素和多因素Cox分析显示,ARGs风险评分和TNM肿瘤分期与HCC患者总生存期相关(均P<0.01)。纳入ARGs风险评分和TNM肿瘤分期的列线图用于预测HCC患者1、3和5年总生存状态具有优秀的预测能力。免疫浸润分析显示,与低风险组比较,高风险组在多数固有免疫细胞和适应免疫细胞浸润水平更高(均P<0.05)。基因本体论(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析显示,高风险组上调基因主要富集于白细胞迁移、细胞运动和分化等多种通路和途径(均P<0.05)。基因组改变差异分析显示,高风险组患者tumor protein p53(TP53)突变频率更高(P=0.003),低风险组患者lysine methyltransferase 2D(KMT2D)突变率更高(P=0.031)。结论本研究建立并验证了基于ARGs的风险评分模型,为预测亚洲人种HCC患者的预后状态提供了一项有效的参考指标。
文摘The author divided the Baimiao crania into crania Ⅰand crania Ⅱ. According to the comparative result, the author thought the main physical features of crania Ⅰbelonged to the Eastern Asiatic Mongoloid,Crania Ⅱ belongs to the Northern Asi atic Mongoloid. The main physical features of crania Ⅰ are mostly similar to those of modern people in northe China. Crania Ⅱ is mostly similar th the modern Mon golian, modern people of north and south China are followed. The main physical fea tures of crania Ⅰ are mostly similar to those of the Xiajiadian upper layer culture,crania Ⅱ is similar to the crania A of Maoqinggou-Yinniugon and Guoxianyaozi cra nia. The author thought the population lived in it should belong to the "Dai"nation which existed during the Spring Autumnand Waring States Period, its nationality may be belong to the ancientn"Di"
