目的研究G_(2)/S期应答相关蛋白1(G_(2) and S phase-expressed protein 1,GTSE1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达、免疫学作用和预后分析,及其潜在作用机制。方法使用公共数据库癌症基因组图谱(The Cancer Genome At...目的研究G_(2)/S期应答相关蛋白1(G_(2) and S phase-expressed protein 1,GTSE1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达、免疫学作用和预后分析,及其潜在作用机制。方法使用公共数据库癌症基因组图谱(The Cancer Genome Atlas,TCGA)提供的数据,用Kaplan-Meier、肿瘤免疫评估资源(Tumor Immune Estimation Resource,TIMER)数据库和基因表达谱交互分析(Gene Expression Profiling Interactive Analysis,GEPIA)数据库进行GTSE1基因表达、免疫学作用及预后分析,通过免疫组化实验验证GTSE1在临床样本中的表达,应用R软件对GTSE1相关差异基因进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。结果GTSE1在人类癌组织中显著高表达,且与肝细胞癌预后不良显著相关(P<0.05);GTSE1基因表达与HCC中浸润性免疫细胞的丰度显著相关(P<0.001)。GTSE1相关的差异表达基因主要富集于核分裂、细胞器裂变、离子通道活性等基因模块;其参与的信号通路主要包括神经活性配体-受体的相互作用、细胞周期等。结论GTSE1在HCC中的表达显著上调并与患者预后不良显著相关,且在免疫细胞浸润中发挥重要作用,可作为HCC的预后标志物和免疫治疗靶点。展开更多
目的:探究外周血单个核细胞G_(2)/S期应答相关蛋白1(G_(2)and S phase-expressed-1,GTSE1)水平与上皮性卵巢癌(epithelial ovarian cancer,EOC)预后的关系。方法:GEPIA和Kaplan-Meier Plotter分析GTSE1在卵巢癌组织中的表达及其与预后...目的:探究外周血单个核细胞G_(2)/S期应答相关蛋白1(G_(2)and S phase-expressed-1,GTSE1)水平与上皮性卵巢癌(epithelial ovarian cancer,EOC)预后的关系。方法:GEPIA和Kaplan-Meier Plotter分析GTSE1在卵巢癌组织中的表达及其与预后的关系。选择2017年04月至2020年10月本院126例EOC患者(EOC组)和40例同期无EOC的健康体检者(对照组)作为研究对象。Ficoll密度梯度离心法分离外周血中单个核细胞,蛋白质免疫印迹法检测GTSE1水平。Spearman相关分析EOC组织和外周血单个核细胞中GTSE1水平的关系。随访了解EOC预后,用COX回归分析EOC预后的风险因素。结果:GEPIA和Kaplan-Meier Plotter分析结果显示,卵巢癌组织中GTSE1水平高于正常卵巢组织(P<0.05),GTSE1低水平卵巢癌患者的中位无进展生存时间高于GTSE1高水平卵巢癌患者(P<0.05)。随访期间复发98例(77.8%),其中铂类敏感型65例,铂类耐药型33例;死亡41例(32.5%)。EOC组的外周血单个核细胞中GTSE1 mRNA和GTSE1蛋白水平均高于对照组(P<0.001)。EOC患者癌组织和外周血单个核细胞中GTSE1水平呈正相关关系(r_(s)=0.225,P=0.011)。国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)Ⅰ-Ⅱ期患者的GTSE1水平低于Ⅲ-Ⅳ期的患者(P<0.001);未复发患者的GTSE1水平低于铂类敏感型和铂类耐药型的患者(P<0.05);生存患者的GTSE1水平低于死亡患者(P<0.001)。GTSE1高水平患者的无复发生存时间和总生存时间均低于GTSE1低水平患者(P<0.001)。COX回归分析结果显示,FIGO分期高(HR=2.110,95%CI:1.465~3.038,P<0.001;HR=2.261,95%CI:1.212~4.216,P=0.011)、初次手术残存灶>1 cm(HR=1.724,95%CI:1.130~2.631,P=0.012;HR=2.465,95%CI:1.246~4.874,P=0.010)和GTSE1>1.29(HR=2.071,95%CI:1.304~3.291,P=0.002;HR=5.634,95%CI:2.410~13.169,P<0.001)是EOC预后(复发和生存)的独立危险因素,应用贝伐单抗(HR=0.293,95%CI:0.116~0.738,P=0.010;HR=0.141,95%CI:0.056~0.357,P<0.001)是EOC预后的独立保护因素。结论:EOC患者外周血单个核细胞中GTSE1水平高提示预后不良风险高。展开更多
Space-filling designs are widely used in computer experiments.They are frequently evaluated by the orthogonality and distance-related criteria.Rotating orthogonal arrays is an appealing approach to constructing orthog...Space-filling designs are widely used in computer experiments.They are frequently evaluated by the orthogonality and distance-related criteria.Rotating orthogonal arrays is an appealing approach to constructing orthogonal space-filling designs.An important issue that has been rarely addressed in the literature is the design selection for the initial orthogonal arrays.This paper studies the maximin L_(2)-distance properties of orthogonal designs generated by rotating two-level orthogonal arrays under three criteria.We provide theoretical justifications for the rotation method from a maximin distance perspective and further propose to select initial orthogonal arrays by the minimum G_(2)-aberration criterion.New infinite families of orthogonal or 3-orthogonal U-type designs,which also perform well under the maximin distance criterion,are obtained and tabulated.Examples are presented to show the effectiveness of the constructed designs for building statistical surrogate models.展开更多
文摘目的研究G_(2)/S期应答相关蛋白1(G_(2) and S phase-expressed protein 1,GTSE1)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达、免疫学作用和预后分析,及其潜在作用机制。方法使用公共数据库癌症基因组图谱(The Cancer Genome Atlas,TCGA)提供的数据,用Kaplan-Meier、肿瘤免疫评估资源(Tumor Immune Estimation Resource,TIMER)数据库和基因表达谱交互分析(Gene Expression Profiling Interactive Analysis,GEPIA)数据库进行GTSE1基因表达、免疫学作用及预后分析,通过免疫组化实验验证GTSE1在临床样本中的表达,应用R软件对GTSE1相关差异基因进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。结果GTSE1在人类癌组织中显著高表达,且与肝细胞癌预后不良显著相关(P<0.05);GTSE1基因表达与HCC中浸润性免疫细胞的丰度显著相关(P<0.001)。GTSE1相关的差异表达基因主要富集于核分裂、细胞器裂变、离子通道活性等基因模块;其参与的信号通路主要包括神经活性配体-受体的相互作用、细胞周期等。结论GTSE1在HCC中的表达显著上调并与患者预后不良显著相关,且在免疫细胞浸润中发挥重要作用,可作为HCC的预后标志物和免疫治疗靶点。
文摘目的:探究外周血单个核细胞G_(2)/S期应答相关蛋白1(G_(2)and S phase-expressed-1,GTSE1)水平与上皮性卵巢癌(epithelial ovarian cancer,EOC)预后的关系。方法:GEPIA和Kaplan-Meier Plotter分析GTSE1在卵巢癌组织中的表达及其与预后的关系。选择2017年04月至2020年10月本院126例EOC患者(EOC组)和40例同期无EOC的健康体检者(对照组)作为研究对象。Ficoll密度梯度离心法分离外周血中单个核细胞,蛋白质免疫印迹法检测GTSE1水平。Spearman相关分析EOC组织和外周血单个核细胞中GTSE1水平的关系。随访了解EOC预后,用COX回归分析EOC预后的风险因素。结果:GEPIA和Kaplan-Meier Plotter分析结果显示,卵巢癌组织中GTSE1水平高于正常卵巢组织(P<0.05),GTSE1低水平卵巢癌患者的中位无进展生存时间高于GTSE1高水平卵巢癌患者(P<0.05)。随访期间复发98例(77.8%),其中铂类敏感型65例,铂类耐药型33例;死亡41例(32.5%)。EOC组的外周血单个核细胞中GTSE1 mRNA和GTSE1蛋白水平均高于对照组(P<0.001)。EOC患者癌组织和外周血单个核细胞中GTSE1水平呈正相关关系(r_(s)=0.225,P=0.011)。国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)Ⅰ-Ⅱ期患者的GTSE1水平低于Ⅲ-Ⅳ期的患者(P<0.001);未复发患者的GTSE1水平低于铂类敏感型和铂类耐药型的患者(P<0.05);生存患者的GTSE1水平低于死亡患者(P<0.001)。GTSE1高水平患者的无复发生存时间和总生存时间均低于GTSE1低水平患者(P<0.001)。COX回归分析结果显示,FIGO分期高(HR=2.110,95%CI:1.465~3.038,P<0.001;HR=2.261,95%CI:1.212~4.216,P=0.011)、初次手术残存灶>1 cm(HR=1.724,95%CI:1.130~2.631,P=0.012;HR=2.465,95%CI:1.246~4.874,P=0.010)和GTSE1>1.29(HR=2.071,95%CI:1.304~3.291,P=0.002;HR=5.634,95%CI:2.410~13.169,P<0.001)是EOC预后(复发和生存)的独立危险因素,应用贝伐单抗(HR=0.293,95%CI:0.116~0.738,P=0.010;HR=0.141,95%CI:0.056~0.357,P<0.001)是EOC预后的独立保护因素。结论:EOC患者外周血单个核细胞中GTSE1水平高提示预后不良风险高。
基金supported by National Natural Science Foundation of China(Grant Nos.11901199 and 71931004),supported by National Natural Science Foundation of China(Grant Nos.11971098 and 11471069)the Open Research Fund of Key Laboratory for Applied Statistics of Ministry of Education,Northeast Normal University(Grant No.130028906)+1 种基金Shanghai Chenguang Program(Grant No.19CG26)National Key R&D Program of China(Grant No.2020YFA0714102)。
文摘Space-filling designs are widely used in computer experiments.They are frequently evaluated by the orthogonality and distance-related criteria.Rotating orthogonal arrays is an appealing approach to constructing orthogonal space-filling designs.An important issue that has been rarely addressed in the literature is the design selection for the initial orthogonal arrays.This paper studies the maximin L_(2)-distance properties of orthogonal designs generated by rotating two-level orthogonal arrays under three criteria.We provide theoretical justifications for the rotation method from a maximin distance perspective and further propose to select initial orthogonal arrays by the minimum G_(2)-aberration criterion.New infinite families of orthogonal or 3-orthogonal U-type designs,which also perform well under the maximin distance criterion,are obtained and tabulated.Examples are presented to show the effectiveness of the constructed designs for building statistical surrogate models.