目的:探究G2/S期表达蛋白1(G2 and S phase-expressed protein1,GTSE1)在肺腺癌中的表达情况以及对预后的影响。方法:从癌症基因组图谱(TCGA)数据库中下载肺腺癌患者表达谱数据以及临床信息资料,分析GTSE1表达水平与临床指标信息之间的...目的:探究G2/S期表达蛋白1(G2 and S phase-expressed protein1,GTSE1)在肺腺癌中的表达情况以及对预后的影响。方法:从癌症基因组图谱(TCGA)数据库中下载肺腺癌患者表达谱数据以及临床信息资料,分析GTSE1表达水平与临床指标信息之间的相关性及对预后的影响,并用Cox比例风险回归模型分析影响患者预后的因素。采用免疫组化检测14例肺腺癌肿瘤组织和13例癌旁组织中GTSE1表达水平。采用基因集富集分析方法(GSEA)预测GTSE1在肺腺癌中可能参与并调控的相关通路。结果:在TCGA数据中,在肿瘤组织样本中GTSE1基因表达情况明显高于正常组织(t=18.165,P<0.05),且表达水平与肿瘤分级(χ^(2)=17.543,P=0.001)、T(χ^(2)=8.825,P=0.032)和N分期(χ^(2)=12.138,P=0.001)之间有显著相关,GTSE1高表达患者的总生存期显著低于GTSE1低表达的患者(χ^(2)=22.663,P<0.05),单因素Cox分析提示肿瘤分级(HR=1.56,95%CI:1.33~1.83)、TNM分期(T:HR=1.60,95%CI:1.31~1.95;N:HR=1.70,95%CI:1.40~2.06;M:HR=1.83,95%CI:1.03~3.25)和GTSE1表达水平(HR=2.32,95%CI:1.62~3.30)可影响患者的总生存期(均P<0.05)。多因素Cox分析提示T分期(HR=1.646,95%CI:1.038~2.610,P=0.034)和GTSE1的表达水平(HR=1.830,95%CI:1.269~2.637,P<0.05)是影响肺腺癌患者总生存期的独立危险因素。GTSE1基因高表达的样本在细胞周期以及p53信号通路等9个通路基因集中富集(P<0.05,FDR<0.01)。结论:GTSE1在肺腺癌患者肿瘤组织中显著高表达,是肺腺癌患者的独立预后因素。展开更多
目的:验证G2/S期应答相关蛋白1(G2 and S phase-expressed protein 1,GTSE1)在原发性肝癌组织及细胞株中高表达,并探讨其表达下调对肝癌细胞凋亡的影响。方法:采用内置R程序对GEO(Gene Expression Omnibus)数据库中4项原发性肝癌临床研...目的:验证G2/S期应答相关蛋白1(G2 and S phase-expressed protein 1,GTSE1)在原发性肝癌组织及细胞株中高表达,并探讨其表达下调对肝癌细胞凋亡的影响。方法:采用内置R程序对GEO(Gene Expression Omnibus)数据库中4项原发性肝癌临床研究的基因表达矩阵数据进行分析,筛选肝癌与癌旁组织差异表达基因。采用蛋白质印迹法验证3例肝癌组织和3株肝癌细胞中GTSE1蛋白表达水平。向肝癌Hep-G2和Bel-7402细胞中分别转染GTSE1 siRNA后,采用CCK-8和FCM法分别检测GTSE1表达下调对肝癌细胞增殖、凋亡及5-氟尿嘧啶(5-fluorouracil,5-FU)敏感性的影响,进一步采用蛋白质印迹法检测p53含量及其亚细胞定位,以及Bcl-2家族成员的表达变化。结果:4项研究中原发性肝癌组织表达水平均上调和下调的基因分别为51和146个。其中,上调基因产物GTSE1蛋白在3例临床肝癌组织标本和3株肝癌细胞Hep-G2、Bel-7402和SMMC-7721中均得到进一步验证(P值均<0.001)。siRNA转染后,肝癌Hep-G2和Bel-7402细胞中GTSE1基因沉默效率>70%。与对照组相比,GTSE1表达下调后肝癌Hep-G2和Bel-7402细胞增殖被明显抑制,并随着时间延长,抑制作用逐渐增强(P值均<0.05);GTSE1表达下调后肝癌Hep-G2和Bel-7402细胞周期被阻滞在G1期,同时细胞凋亡率明显升高,且细胞对5-FU的敏感性明显增强(P值均<0.01)。GTSE1表达下调后的肝癌Hep-G2和Bel-7402细胞中总p53及磷酸化P53表达水平均明显上调(P值均<0.05),且细胞核内p53水平升高(P值均<0.01);Bcl-2家族促凋亡成员Bax和Bak表达水平均上调,而抗凋亡成员Bcl-2表达水平下调(P值均<0.05)。结论:下调肝癌中GTSE1蛋白表达能通过活化p53通路促进细胞凋亡,并增加肝癌细胞对化疗药物的敏感性。展开更多
Understanding metastatic osteosarcoma relies on defining the complexity of cell types,their associated molecular profiles,and interactions among cells in the tumor microenvironment.Here,we integrated single-cell and b...Understanding metastatic osteosarcoma relies on defining the complexity of cell types,their associated molecular profiles,and interactions among cells in the tumor microenvironment.Here,we integrated single-cell and bulk gene expression datasets and revealed that metastatic lesions were highly enriched for GTSE1+osteoblasts(OB).Under the regulation of E2F family members,GTSE1+OB cells harbored enhanced proliferation activity and high differentiation potential.Augmentation of GTSE1 enhanced the abilities of cell migration and invasion,while silencing of GTSE1 impaired the abilities in human OB cell lines.Furthermore,cellular communication analysis showed the cross-talk between GTSE1+OB cells and CD8+T cells in metastasis was achieved through the MIF-(CD74-CXCR4)pair.Spatial transcriptomic data revealed that MIF-CD74 and CXCR4-MIF/CD74 showed a higher positive correlation in undifferentiated pleomorphic sarcoma than leiomyosarcoma.Correlation analysis unveiled that GTSE1+OB cells and monocytes were the negatively correlated populations at the single-cell level,a finding validated in 4 independent osteosarcoma datasets comprising 226 samples.Our findings suggest that GTSE1 overexpression serves as a potential biomarker for metastasis in osteosarcoma and provides a promising strategy to prevent metastasis by targeting GTSE1+OB cells.展开更多
文摘目的:探究G2/S期表达蛋白1(G2 and S phase-expressed protein1,GTSE1)在肺腺癌中的表达情况以及对预后的影响。方法:从癌症基因组图谱(TCGA)数据库中下载肺腺癌患者表达谱数据以及临床信息资料,分析GTSE1表达水平与临床指标信息之间的相关性及对预后的影响,并用Cox比例风险回归模型分析影响患者预后的因素。采用免疫组化检测14例肺腺癌肿瘤组织和13例癌旁组织中GTSE1表达水平。采用基因集富集分析方法(GSEA)预测GTSE1在肺腺癌中可能参与并调控的相关通路。结果:在TCGA数据中,在肿瘤组织样本中GTSE1基因表达情况明显高于正常组织(t=18.165,P<0.05),且表达水平与肿瘤分级(χ^(2)=17.543,P=0.001)、T(χ^(2)=8.825,P=0.032)和N分期(χ^(2)=12.138,P=0.001)之间有显著相关,GTSE1高表达患者的总生存期显著低于GTSE1低表达的患者(χ^(2)=22.663,P<0.05),单因素Cox分析提示肿瘤分级(HR=1.56,95%CI:1.33~1.83)、TNM分期(T:HR=1.60,95%CI:1.31~1.95;N:HR=1.70,95%CI:1.40~2.06;M:HR=1.83,95%CI:1.03~3.25)和GTSE1表达水平(HR=2.32,95%CI:1.62~3.30)可影响患者的总生存期(均P<0.05)。多因素Cox分析提示T分期(HR=1.646,95%CI:1.038~2.610,P=0.034)和GTSE1的表达水平(HR=1.830,95%CI:1.269~2.637,P<0.05)是影响肺腺癌患者总生存期的独立危险因素。GTSE1基因高表达的样本在细胞周期以及p53信号通路等9个通路基因集中富集(P<0.05,FDR<0.01)。结论:GTSE1在肺腺癌患者肿瘤组织中显著高表达,是肺腺癌患者的独立预后因素。
文摘目的:验证G2/S期应答相关蛋白1(G2 and S phase-expressed protein 1,GTSE1)在原发性肝癌组织及细胞株中高表达,并探讨其表达下调对肝癌细胞凋亡的影响。方法:采用内置R程序对GEO(Gene Expression Omnibus)数据库中4项原发性肝癌临床研究的基因表达矩阵数据进行分析,筛选肝癌与癌旁组织差异表达基因。采用蛋白质印迹法验证3例肝癌组织和3株肝癌细胞中GTSE1蛋白表达水平。向肝癌Hep-G2和Bel-7402细胞中分别转染GTSE1 siRNA后,采用CCK-8和FCM法分别检测GTSE1表达下调对肝癌细胞增殖、凋亡及5-氟尿嘧啶(5-fluorouracil,5-FU)敏感性的影响,进一步采用蛋白质印迹法检测p53含量及其亚细胞定位,以及Bcl-2家族成员的表达变化。结果:4项研究中原发性肝癌组织表达水平均上调和下调的基因分别为51和146个。其中,上调基因产物GTSE1蛋白在3例临床肝癌组织标本和3株肝癌细胞Hep-G2、Bel-7402和SMMC-7721中均得到进一步验证(P值均<0.001)。siRNA转染后,肝癌Hep-G2和Bel-7402细胞中GTSE1基因沉默效率>70%。与对照组相比,GTSE1表达下调后肝癌Hep-G2和Bel-7402细胞增殖被明显抑制,并随着时间延长,抑制作用逐渐增强(P值均<0.05);GTSE1表达下调后肝癌Hep-G2和Bel-7402细胞周期被阻滞在G1期,同时细胞凋亡率明显升高,且细胞对5-FU的敏感性明显增强(P值均<0.01)。GTSE1表达下调后的肝癌Hep-G2和Bel-7402细胞中总p53及磷酸化P53表达水平均明显上调(P值均<0.05),且细胞核内p53水平升高(P值均<0.01);Bcl-2家族促凋亡成员Bax和Bak表达水平均上调,而抗凋亡成员Bcl-2表达水平下调(P值均<0.05)。结论:下调肝癌中GTSE1蛋白表达能通过活化p53通路促进细胞凋亡,并增加肝癌细胞对化疗药物的敏感性。
基金supported by the National Key Research and Development Program of China(No.2023YFF1204600 to Lei Yang)the National Natural Science Foundation of China(No.81972117 to Lei Yang,32270710 to Yunyan Gu)+2 种基金the Natural Science Foundation of Heilongjiang Province,China(No.JQ2020H001 to Lei Yang)the Key R&D Program of Heilongjiang Province,China(No.GA23C002 to Lei Yang)the First Affiliated Hospital of Harbin Medical University Excellent Young Talents Funding,China(No.HYD2020JQ0013 to Lei Yang).
文摘Understanding metastatic osteosarcoma relies on defining the complexity of cell types,their associated molecular profiles,and interactions among cells in the tumor microenvironment.Here,we integrated single-cell and bulk gene expression datasets and revealed that metastatic lesions were highly enriched for GTSE1+osteoblasts(OB).Under the regulation of E2F family members,GTSE1+OB cells harbored enhanced proliferation activity and high differentiation potential.Augmentation of GTSE1 enhanced the abilities of cell migration and invasion,while silencing of GTSE1 impaired the abilities in human OB cell lines.Furthermore,cellular communication analysis showed the cross-talk between GTSE1+OB cells and CD8+T cells in metastasis was achieved through the MIF-(CD74-CXCR4)pair.Spatial transcriptomic data revealed that MIF-CD74 and CXCR4-MIF/CD74 showed a higher positive correlation in undifferentiated pleomorphic sarcoma than leiomyosarcoma.Correlation analysis unveiled that GTSE1+OB cells and monocytes were the negatively correlated populations at the single-cell level,a finding validated in 4 independent osteosarcoma datasets comprising 226 samples.Our findings suggest that GTSE1 overexpression serves as a potential biomarker for metastasis in osteosarcoma and provides a promising strategy to prevent metastasis by targeting GTSE1+OB cells.
