目的·研究丝氨酸蛋白酶抑制因子1(serpin family E member 1,SERPINE1)在胃癌中的表达及其促进胃癌发展的潜在作用机制。方法·使用TIMER2.0在线网站对SERPINE1进行泛癌分析,通过癌症基因组图谱(The Cancer Genome Atlas,TCGA...目的·研究丝氨酸蛋白酶抑制因子1(serpin family E member 1,SERPINE1)在胃癌中的表达及其促进胃癌发展的潜在作用机制。方法·使用TIMER2.0在线网站对SERPINE1进行泛癌分析,通过癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中的胃癌临床数据分析SERPINE1在不同胃癌肿瘤分期样本中的表达差异并绘制生存曲线。采用实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)检测临床胃癌组织配对样本中SERPINE1 mRNA的表达情况。小干扰RNA(small interfering RNA,siRNA)转染技术敲低MGC-803、SGC-7901胃癌细胞系中SERPINE1表达,通过Transwell和Invasion小室实验检测胃癌细胞迁移、侵袭能力;进一步通过人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVEC)迁移实验和小管形成实验探究敲低SERPINE1对胃癌细胞血管生成能力的影响。利用基因表达综合(Gene Expression Omnibus,GEO)数据集,根据SERPINE1的表达水平中位值分为高表达和低表达2组进行差异基因分析,并进行京都基因与基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析和基因集富集分析(Gene Set EnrichmentAnalysis,GSEA);进一步通过qRT-PCR验证SERPINE1敲低胃癌细胞系上皮-间充质转化(epithelial-mesenchymal transition,EMT)、血管生成有关的关键基因表达水平。结果·生物信息学分析显示,SERPINE1在包括胃癌在内的多种原发肿瘤组织中高表达,SERPINE1基因表达随着肿瘤分期的增加而升高(P<0.001),SERPINE1表达增加与胃癌不良预后有关(P<0.001)。qRT-PCR结果表明SERPINE1在胃癌组织中明显高表达(P=0.038)。敲低SERPINE1后,胃癌细胞系MGC-803、SGC-7901细胞迁移和侵袭能力下降(P<0.05);敲低SERPINE1的胃癌细胞系的培养上清液能降低HUVEC细胞迁移和小管生成能力(P<0.05)。GEO数据库中SERPINE1高表达组胃癌患者差异基因富集到焦点黏附、细胞外基质受体相互作用等癌症相关通路以及血管生成、血管内皮生长因子信号等血管生成相关通路。SERPINE1的表达与E-钙黏蛋白(cadherin 1,CDH1)的表达呈负相关,与EMT有关的其他基因、血管生成有关基因的表达均呈正相关。利用qRT-PCR在SERPINE1敲低胃癌细胞系中验证了EMT(P<0.05)、血管生成有关基因表达水平(P<0.05),与上述相关性分析结果一致。结论·SERPINE1在胃癌组织中表达升高,可调控EMT、血管生成相关关键基因的表达水平并促进胃癌细胞迁移、侵袭与血管生成。展开更多
研究利用孟德尔随机化法(Mendelian randomization, MR)分析了几种食源性病原体与白细胞分化抗原44 (Cluster of differentiation 44, CD44)之间的关联,CD44抗原是胃肠道癌症发展和转移的标志物。该研究从综合流行病学数据库(IEU)、芬...研究利用孟德尔随机化法(Mendelian randomization, MR)分析了几种食源性病原体与白细胞分化抗原44 (Cluster of differentiation 44, CD44)之间的关联,CD44抗原是胃肠道癌症发展和转移的标志物。该研究从综合流行病学数据库(IEU)、芬兰基因数据库(FinnGen)和英国生物数据库(UK Biobank)获得了全基因组关联研究(Genome-wide association studies, GWAS)数据,并主要使用反方差加权(Inverse-variance weighting, IVW)等统计方法分析了相关性。同时还进行了敏感性分析,以提高结果的可靠性。研究结果表明,幽门螺旋杆菌与CD44抗原呈显著正相关,而小肠结肠耶尔森氏菌与CD44抗原呈显著性负相关,因此研究判断幽门螺旋杆菌会促进癌症的发生和转移,而小肠结肠耶尔森氏菌可抑制癌细胞的发展和转移。然而,其余细菌种类没有发现明显的相关性。部分食源性致病菌可能会促进胃肠道癌症的转移,如幽门螺旋杆菌。但还有些可能抑制了癌细胞的转移,表明背后可能有更复杂的生理机制。This study used Mendelian randomization (MR) to analyze the association between several foodborne pathogens and the Cluster of Differentiation 44 (CD44) antigen, a marker of gastrointestinal cancer development and metastasis. The study obtained genome-wide association studies (GWAS) data from Integrative Epidemiology Unit (IEU), FinnGen and UK Biobank and analyzed the correlation mainly using statistical methods such as inverse-variance weighted (IVW). Sensitivity analyses were also carried out to improve the reliability of the results. The results of the study showed that Helicobacter pylori showed a significant positive correlation with CD44 antigen;Yersinia enterocolitica showed a significant negative correlation with CD44 antigen;therefore, we judged that Helicobacter pylori promotes cancer development and metastasis, and Yersinia enterocolitica inhibits cancer cell development and metastasis. However, no significant correlation was found for the remaining bacterial species. Some foodborne pathogens, such as Helicobacter pylori, can promote the metastasis of gastrointestinal cancers. However, others can inhibit the metastasis of cancer cells, suggesting that there may be a more complex physiological mechanism involved.展开更多
文摘目的·研究丝氨酸蛋白酶抑制因子1(serpin family E member 1,SERPINE1)在胃癌中的表达及其促进胃癌发展的潜在作用机制。方法·使用TIMER2.0在线网站对SERPINE1进行泛癌分析,通过癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中的胃癌临床数据分析SERPINE1在不同胃癌肿瘤分期样本中的表达差异并绘制生存曲线。采用实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)检测临床胃癌组织配对样本中SERPINE1 mRNA的表达情况。小干扰RNA(small interfering RNA,siRNA)转染技术敲低MGC-803、SGC-7901胃癌细胞系中SERPINE1表达,通过Transwell和Invasion小室实验检测胃癌细胞迁移、侵袭能力;进一步通过人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVEC)迁移实验和小管形成实验探究敲低SERPINE1对胃癌细胞血管生成能力的影响。利用基因表达综合(Gene Expression Omnibus,GEO)数据集,根据SERPINE1的表达水平中位值分为高表达和低表达2组进行差异基因分析,并进行京都基因与基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析和基因集富集分析(Gene Set EnrichmentAnalysis,GSEA);进一步通过qRT-PCR验证SERPINE1敲低胃癌细胞系上皮-间充质转化(epithelial-mesenchymal transition,EMT)、血管生成有关的关键基因表达水平。结果·生物信息学分析显示,SERPINE1在包括胃癌在内的多种原发肿瘤组织中高表达,SERPINE1基因表达随着肿瘤分期的增加而升高(P<0.001),SERPINE1表达增加与胃癌不良预后有关(P<0.001)。qRT-PCR结果表明SERPINE1在胃癌组织中明显高表达(P=0.038)。敲低SERPINE1后,胃癌细胞系MGC-803、SGC-7901细胞迁移和侵袭能力下降(P<0.05);敲低SERPINE1的胃癌细胞系的培养上清液能降低HUVEC细胞迁移和小管生成能力(P<0.05)。GEO数据库中SERPINE1高表达组胃癌患者差异基因富集到焦点黏附、细胞外基质受体相互作用等癌症相关通路以及血管生成、血管内皮生长因子信号等血管生成相关通路。SERPINE1的表达与E-钙黏蛋白(cadherin 1,CDH1)的表达呈负相关,与EMT有关的其他基因、血管生成有关基因的表达均呈正相关。利用qRT-PCR在SERPINE1敲低胃癌细胞系中验证了EMT(P<0.05)、血管生成有关基因表达水平(P<0.05),与上述相关性分析结果一致。结论·SERPINE1在胃癌组织中表达升高,可调控EMT、血管生成相关关键基因的表达水平并促进胃癌细胞迁移、侵袭与血管生成。
文摘研究利用孟德尔随机化法(Mendelian randomization, MR)分析了几种食源性病原体与白细胞分化抗原44 (Cluster of differentiation 44, CD44)之间的关联,CD44抗原是胃肠道癌症发展和转移的标志物。该研究从综合流行病学数据库(IEU)、芬兰基因数据库(FinnGen)和英国生物数据库(UK Biobank)获得了全基因组关联研究(Genome-wide association studies, GWAS)数据,并主要使用反方差加权(Inverse-variance weighting, IVW)等统计方法分析了相关性。同时还进行了敏感性分析,以提高结果的可靠性。研究结果表明,幽门螺旋杆菌与CD44抗原呈显著正相关,而小肠结肠耶尔森氏菌与CD44抗原呈显著性负相关,因此研究判断幽门螺旋杆菌会促进癌症的发生和转移,而小肠结肠耶尔森氏菌可抑制癌细胞的发展和转移。然而,其余细菌种类没有发现明显的相关性。部分食源性致病菌可能会促进胃肠道癌症的转移,如幽门螺旋杆菌。但还有些可能抑制了癌细胞的转移,表明背后可能有更复杂的生理机制。This study used Mendelian randomization (MR) to analyze the association between several foodborne pathogens and the Cluster of Differentiation 44 (CD44) antigen, a marker of gastrointestinal cancer development and metastasis. The study obtained genome-wide association studies (GWAS) data from Integrative Epidemiology Unit (IEU), FinnGen and UK Biobank and analyzed the correlation mainly using statistical methods such as inverse-variance weighted (IVW). Sensitivity analyses were also carried out to improve the reliability of the results. The results of the study showed that Helicobacter pylori showed a significant positive correlation with CD44 antigen;Yersinia enterocolitica showed a significant negative correlation with CD44 antigen;therefore, we judged that Helicobacter pylori promotes cancer development and metastasis, and Yersinia enterocolitica inhibits cancer cell development and metastasis. However, no significant correlation was found for the remaining bacterial species. Some foodborne pathogens, such as Helicobacter pylori, can promote the metastasis of gastrointestinal cancers. However, others can inhibit the metastasis of cancer cells, suggesting that there may be a more complex physiological mechanism involved.
