目的应用生物信息学方法探讨鞘氨醇-1-磷酸转运体2(sphingosine-1-phosphate transporter 2,SPNS2)在乳腺癌中的表达情况,并分析SPNS2对乳腺癌预后、诊断或免疫浸润的影响。方法癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库检...目的应用生物信息学方法探讨鞘氨醇-1-磷酸转运体2(sphingosine-1-phosphate transporter 2,SPNS2)在乳腺癌中的表达情况,并分析SPNS2对乳腺癌预后、诊断或免疫浸润的影响。方法癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库检索乳腺癌组织和非乳腺癌样本中的SPNS2 mRNA差异表达数据,并分析SPNS2与乳腺癌之间的关系。用Cox单因素及多因素模型分析SPNS2 mRNA表达对乳腺癌预后的影响。使用Kaplan-Meier曲线评估SPNS2基因的表达与存活率之间的相关性,分析SPNS2对乳腺癌患者生存预后的影响。使用受试者工作特征曲线(receiver operating characteristic,ROC)分析SPNS2对乳腺癌的诊断效能。使用肿瘤免疫估算资源(Tumor Immune Estimation Resource,TIMER)数据库分析SPNS2表达与乳腺癌免疫微环境中不同类型免疫细胞的相关性。搜索相互作用基因检索的工具(Search Tool for the Retrieval of Interacting Genes,STRING)数据库分析乳腺癌中SPNS2与相关蛋白质之间的相互作用。分析京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)数据库中得到的差异基因富集的信号通路。提取正常乳腺上皮细胞和乳腺癌细胞系RNA,通过RT-qPCR实验比较SPNS2的表达水平。结果在TCGA乳腺癌数据库中,SPNS2在乳腺癌组织中表达水平显著低于癌旁组织(P<0.001),SPNS2 mRNA的表达与T、M分期、病理分期、PAM50分型、年龄和组织学类型等因素相关(P<0.05);Cox分析表明年龄>60岁、T4期、M1期等因素是乳腺癌发生预后不良的风险因素(P<0.01);Kaplan-Meier分析显示低表达SPNS2乳腺癌患者具有更长的疾病特异生存期(disease-specific survival,DSS)和无进展间隔期(progression-free interval,PFI)(P<0.05);ROC曲线提示SPNS2诊断具有较好的敏感性和特异性。TIMER数据库分析显示在Luminal型乳腺癌中,SPNS2与CD4+T细胞,巨噬细胞、中性粒细胞等免疫细胞呈正相关(P<0.05)。STRING和KEGG数据库分析表明SPNS2相关蛋白富集于细胞周期和PPAR信号传导等途径(P<0.05)。RT-qPCR实验结果显示与正常乳腺上皮细胞相比,SPNS2在乳腺癌细胞系中低表达(P<0.001)。结论SPNS2是一种潜在的诊断乳腺癌和评价预后的生物学标志物。展开更多
The expanding of material library of laser powder bed fusion(L-PBF)is of great significance to the development of material science.In this study,the biomedical Ti-13Nb-13Zr powder was mixed with the tantalum particles...The expanding of material library of laser powder bed fusion(L-PBF)is of great significance to the development of material science.In this study,the biomedical Ti-13Nb-13Zr powder was mixed with the tantalum particles(2 wt%−8 wt%)and fabricated by L-PBF.The microstructure consists of aβmatrix with partially unmelted pure tantalum distributed along the boundaries of molten pool owing to the Marangoni convention.Because the melting process of Ta absorbs lots of energy,the size of molten pool becomes smaller with the increase of Ta content.The fine microstructure exists in the center of melt pool while coarse microstructure is on the boundaries of melt pool because of the existence of heat-affected zone.The columnar-to-equiaxed transitions(CETs)happen in the zones near the unmelted Ta,and the low lattice mismatch induced by solid Ta phase is responsible for this phenomenon.The recrystallization texture is strengthened while the fiber texture is weakened when the tantalum content is increased.Due to the formation of refined martensiteα′grains during L-PBF,the compressive strengths of L-PBF-processed samples are higher than those fabricated by traditional processing technologies.The present research will provide an important reference for biomedical alloy design via L-PBF process in the future.展开更多
文摘目的应用生物信息学方法探讨鞘氨醇-1-磷酸转运体2(sphingosine-1-phosphate transporter 2,SPNS2)在乳腺癌中的表达情况,并分析SPNS2对乳腺癌预后、诊断或免疫浸润的影响。方法癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库检索乳腺癌组织和非乳腺癌样本中的SPNS2 mRNA差异表达数据,并分析SPNS2与乳腺癌之间的关系。用Cox单因素及多因素模型分析SPNS2 mRNA表达对乳腺癌预后的影响。使用Kaplan-Meier曲线评估SPNS2基因的表达与存活率之间的相关性,分析SPNS2对乳腺癌患者生存预后的影响。使用受试者工作特征曲线(receiver operating characteristic,ROC)分析SPNS2对乳腺癌的诊断效能。使用肿瘤免疫估算资源(Tumor Immune Estimation Resource,TIMER)数据库分析SPNS2表达与乳腺癌免疫微环境中不同类型免疫细胞的相关性。搜索相互作用基因检索的工具(Search Tool for the Retrieval of Interacting Genes,STRING)数据库分析乳腺癌中SPNS2与相关蛋白质之间的相互作用。分析京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)数据库中得到的差异基因富集的信号通路。提取正常乳腺上皮细胞和乳腺癌细胞系RNA,通过RT-qPCR实验比较SPNS2的表达水平。结果在TCGA乳腺癌数据库中,SPNS2在乳腺癌组织中表达水平显著低于癌旁组织(P<0.001),SPNS2 mRNA的表达与T、M分期、病理分期、PAM50分型、年龄和组织学类型等因素相关(P<0.05);Cox分析表明年龄>60岁、T4期、M1期等因素是乳腺癌发生预后不良的风险因素(P<0.01);Kaplan-Meier分析显示低表达SPNS2乳腺癌患者具有更长的疾病特异生存期(disease-specific survival,DSS)和无进展间隔期(progression-free interval,PFI)(P<0.05);ROC曲线提示SPNS2诊断具有较好的敏感性和特异性。TIMER数据库分析显示在Luminal型乳腺癌中,SPNS2与CD4+T细胞,巨噬细胞、中性粒细胞等免疫细胞呈正相关(P<0.05)。STRING和KEGG数据库分析表明SPNS2相关蛋白富集于细胞周期和PPAR信号传导等途径(P<0.05)。RT-qPCR实验结果显示与正常乳腺上皮细胞相比,SPNS2在乳腺癌细胞系中低表达(P<0.001)。结论SPNS2是一种潜在的诊断乳腺癌和评价预后的生物学标志物。
基金Projects(51975061,51775055)supported by the National Natural Science Foundation of ChinaProject(2020JJ5599)supported by the Natural Science Foundation of Hunan Province,ChinaProjects(19C0032,19B033)supported by the Research Foundation of Education Bureau of Hunan Province,China。
文摘The expanding of material library of laser powder bed fusion(L-PBF)is of great significance to the development of material science.In this study,the biomedical Ti-13Nb-13Zr powder was mixed with the tantalum particles(2 wt%−8 wt%)and fabricated by L-PBF.The microstructure consists of aβmatrix with partially unmelted pure tantalum distributed along the boundaries of molten pool owing to the Marangoni convention.Because the melting process of Ta absorbs lots of energy,the size of molten pool becomes smaller with the increase of Ta content.The fine microstructure exists in the center of melt pool while coarse microstructure is on the boundaries of melt pool because of the existence of heat-affected zone.The columnar-to-equiaxed transitions(CETs)happen in the zones near the unmelted Ta,and the low lattice mismatch induced by solid Ta phase is responsible for this phenomenon.The recrystallization texture is strengthened while the fiber texture is weakened when the tantalum content is increased.Due to the formation of refined martensiteα′grains during L-PBF,the compressive strengths of L-PBF-processed samples are higher than those fabricated by traditional processing technologies.The present research will provide an important reference for biomedical alloy design via L-PBF process in the future.
