BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the preval...BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the prevalence of COVID-19 is significantly higher in patients with liver cancer.However,this mechanism of action has not been clarified.Gene sets for COVID-19(GSE180226)and liver cancer(GSE87630)were obtained from the Gene Expression Omnibus database.After identifying the common differentially expressed genes(DEGs)of COVID-19 and liver cancer,functional enrichment analysis,protein-protein interaction network construction and scree-ning and analysis of hub genes were performed.Subsequently,the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed.RESULTS Of 518 common DEGs were obtained by screening for functional analysis.Fifteen hub genes including aurora kinase B,cyclin B2,cell division cycle 20,cell division cycle associated 8,nucleolar and spindle associated protein 1,etc.,were further identified from DEGs using the“cytoHubba”plugin.Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation,cell cycle and other functions,and they may serve as potential molecular markers for COVID-19 and liver cancer.Finally,we selected 10 of the hub genes for in vitro expression validation in liver cancer cells.CONCLUSION Our study reveals a common pathogenesis of liver cancer and COVID-19.These common pathways and key genes may provide new ideas for further mechanistic studies.展开更多
背景与目的:干扰素/维甲酸联合应用诱导细胞凋亡相关的基因(gene associated with retinoid-interferon-induced mortality-19,GRIM-19)属转录信号转导子与激活子3(signal transducers and activators of transcription 3,STAT3)特异性...背景与目的:干扰素/维甲酸联合应用诱导细胞凋亡相关的基因(gene associated with retinoid-interferon-induced mortality-19,GRIM-19)属转录信号转导子与激活子3(signal transducers and activators of transcription 3,STAT3)特异性抑制蛋白,STAT3及其介导的信号转导通路参与调节细胞的增殖、凋亡与分化,并介导细胞的恶性转化。本研究分析GRIM-19及其靶基因STAT3在结直肠癌组织中的表达情况,探讨GRIM-19及其靶基因产物在结直肠癌发病中的作用。方法:采用免疫组织化学染色及Western blot检测40例结直肠正常组织及癌组织中GRIM-19、STAT3、p-STAT3蛋白表达,对各表达情况与不同临床病理特征进行统计学分析。采用逆转录-聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)方法及测序检测结肠癌细胞系SW480及23例结直肠正常组织及癌组织中GRIM-19mRNA有无基因突变及在mRNA的表达情况。结果:在结直肠癌组织中STAT3及p-STAT3蛋白均高表达,而GRIM-19mRNA及蛋白表达在癌组织中明显低于正常组织,且GRIM-19蛋白表达水平与结直肠癌分化程度和临床分期相关(P<0.05)。GRIM-19与STAT3和p-STAT3在结直肠癌组织中表达情况呈负相关,GRIM-19基因阳性时,STAT3基因趋向阴性(χ2=9.95,P<0.01),p-STAT3基因也趋向阴性(χ2=5.10,P=0.02)。结直肠癌组织中GRIM-19mRNA无基因突变情况。结论:GRIM-19蛋白在结直肠癌组织中的低表达或缺失与结直肠癌的发生、发展及侵袭性相关,而与基因突变无关。在结直肠癌组织中存在STAT3的持续高表达和GRIM-19的低表达共存现象,可能与细胞更易发生恶性转化和异常增殖,促进了结直肠癌的发生发展相关。展开更多
背景与目的:维甲酸/干扰素联合应用诱导细胞凋亡相关的基因(gene associated with retinoid-interferon-induced mortality-19,GRIM-19)是死亡相关基因中的一员,它的过高表达可以抑制肿瘤细胞的增殖,促进细胞的凋亡。本研究检测非小细...背景与目的:维甲酸/干扰素联合应用诱导细胞凋亡相关的基因(gene associated with retinoid-interferon-induced mortality-19,GRIM-19)是死亡相关基因中的一员,它的过高表达可以抑制肿瘤细胞的增殖,促进细胞的凋亡。本研究检测非小细胞肺癌和正常肺组织中GRIM-19蛋白的表达和定位,探讨其在非小细胞肺癌组织中表达的临床意义。方法:应用免疫组化ABC法检测49例非小细胞肺癌组织及相应癌旁正常组织中GRIM-19蛋白的表达情况,并用光密度(A)值定量描述其表达水平;同时用激光共聚焦扫描技术检测GRIM-19蛋白在细胞内的定位。结果:正常肺组织中GRIM-19主要定位于细胞浆中;而肿瘤组织主要位于细胞核中。激光共聚焦扫描技术检测验证了这种结果。GRIM-19蛋白在正常肺组织中阳性率为93.8%(46/49),而在非小细胞肺癌中阳性率为55.1%(27/49),两者之间的差异有统计学意义(P<0.01)。肿瘤组织中GRIM-19蛋白的平均表达水平(A值为0.22±0.01)比正常组织(A值为0.29±0.02)下降24.3%(P<0.01)。GRIM-19蛋白阳性率在Ⅰ、Ⅱ、Ⅲ+Ⅳ期非小细胞肺癌组织中分别是78.6%、48.1%、12.5%,其差异有统计学意义(rs=-0.428,P<0.05)。结论:肺癌组织中GRIM-19蛋白表达随肿瘤恶性程度升高而显著下降甚至缺失,分布由胞浆转入细胞核;GRIM-19蛋白表达可能与肺癌的发生发展相关。展开更多
文摘BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the prevalence of COVID-19 is significantly higher in patients with liver cancer.However,this mechanism of action has not been clarified.Gene sets for COVID-19(GSE180226)and liver cancer(GSE87630)were obtained from the Gene Expression Omnibus database.After identifying the common differentially expressed genes(DEGs)of COVID-19 and liver cancer,functional enrichment analysis,protein-protein interaction network construction and scree-ning and analysis of hub genes were performed.Subsequently,the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed.RESULTS Of 518 common DEGs were obtained by screening for functional analysis.Fifteen hub genes including aurora kinase B,cyclin B2,cell division cycle 20,cell division cycle associated 8,nucleolar and spindle associated protein 1,etc.,were further identified from DEGs using the“cytoHubba”plugin.Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation,cell cycle and other functions,and they may serve as potential molecular markers for COVID-19 and liver cancer.Finally,we selected 10 of the hub genes for in vitro expression validation in liver cancer cells.CONCLUSION Our study reveals a common pathogenesis of liver cancer and COVID-19.These common pathways and key genes may provide new ideas for further mechanistic studies.
文摘背景与目的:干扰素/维甲酸联合应用诱导细胞凋亡相关的基因(gene associated with retinoid-interferon-induced mortality-19,GRIM-19)属转录信号转导子与激活子3(signal transducers and activators of transcription 3,STAT3)特异性抑制蛋白,STAT3及其介导的信号转导通路参与调节细胞的增殖、凋亡与分化,并介导细胞的恶性转化。本研究分析GRIM-19及其靶基因STAT3在结直肠癌组织中的表达情况,探讨GRIM-19及其靶基因产物在结直肠癌发病中的作用。方法:采用免疫组织化学染色及Western blot检测40例结直肠正常组织及癌组织中GRIM-19、STAT3、p-STAT3蛋白表达,对各表达情况与不同临床病理特征进行统计学分析。采用逆转录-聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)方法及测序检测结肠癌细胞系SW480及23例结直肠正常组织及癌组织中GRIM-19mRNA有无基因突变及在mRNA的表达情况。结果:在结直肠癌组织中STAT3及p-STAT3蛋白均高表达,而GRIM-19mRNA及蛋白表达在癌组织中明显低于正常组织,且GRIM-19蛋白表达水平与结直肠癌分化程度和临床分期相关(P<0.05)。GRIM-19与STAT3和p-STAT3在结直肠癌组织中表达情况呈负相关,GRIM-19基因阳性时,STAT3基因趋向阴性(χ2=9.95,P<0.01),p-STAT3基因也趋向阴性(χ2=5.10,P=0.02)。结直肠癌组织中GRIM-19mRNA无基因突变情况。结论:GRIM-19蛋白在结直肠癌组织中的低表达或缺失与结直肠癌的发生、发展及侵袭性相关,而与基因突变无关。在结直肠癌组织中存在STAT3的持续高表达和GRIM-19的低表达共存现象,可能与细胞更易发生恶性转化和异常增殖,促进了结直肠癌的发生发展相关。
文摘背景与目的:维甲酸/干扰素联合应用诱导细胞凋亡相关的基因(gene associated with retinoid-interferon-induced mortality-19,GRIM-19)是死亡相关基因中的一员,它的过高表达可以抑制肿瘤细胞的增殖,促进细胞的凋亡。本研究检测非小细胞肺癌和正常肺组织中GRIM-19蛋白的表达和定位,探讨其在非小细胞肺癌组织中表达的临床意义。方法:应用免疫组化ABC法检测49例非小细胞肺癌组织及相应癌旁正常组织中GRIM-19蛋白的表达情况,并用光密度(A)值定量描述其表达水平;同时用激光共聚焦扫描技术检测GRIM-19蛋白在细胞内的定位。结果:正常肺组织中GRIM-19主要定位于细胞浆中;而肿瘤组织主要位于细胞核中。激光共聚焦扫描技术检测验证了这种结果。GRIM-19蛋白在正常肺组织中阳性率为93.8%(46/49),而在非小细胞肺癌中阳性率为55.1%(27/49),两者之间的差异有统计学意义(P<0.01)。肿瘤组织中GRIM-19蛋白的平均表达水平(A值为0.22±0.01)比正常组织(A值为0.29±0.02)下降24.3%(P<0.01)。GRIM-19蛋白阳性率在Ⅰ、Ⅱ、Ⅲ+Ⅳ期非小细胞肺癌组织中分别是78.6%、48.1%、12.5%,其差异有统计学意义(rs=-0.428,P<0.05)。结论:肺癌组织中GRIM-19蛋白表达随肿瘤恶性程度升高而显著下降甚至缺失,分布由胞浆转入细胞核;GRIM-19蛋白表达可能与肺癌的发生发展相关。
