Background:Lung adenocarcinoma,the most prevalent lung cancer subtype,is increasingly diagnosed in non-smokers and females.The cell cycle regulator CDC20(Cell Division Cycle 20),a crucial activator of the Anaphase-Pro...Background:Lung adenocarcinoma,the most prevalent lung cancer subtype,is increasingly diagnosed in non-smokers and females.The cell cycle regulator CDC20(Cell Division Cycle 20),a crucial activator of the Anaphase-Promoting Complex/Cyclosome(APC/C),is frequently overexpressed in various cancers,including lung adenocarcinoma,and is implicated in tumorigenesis.Preclinical studies indicate that inhibiting the CDC20-APC/C signaling axis can enhance chemotherapy-induced apoptosis.Analysis of The Cancer Genome Atlas(TCGA)data confirms that elevated CDC20 expression in lung adenocarcinoma is significantly associated with poorer patient prognosis and correlates with immune cell infiltration.These collective findings highlight CDC20 as a promising prognostic biomarker and a potential novel therapeutic target for lung adenocarcinoma.Methods:We collected 539 patients with LUAD and 59 normal controls of clinical data from the Cancer Genome Atlas(TCGA)for bioinformatics analysis to investigate the role of CDC20 in LUAD and address the above questions.We evaluated the association between CDC20 expression and clinicopathological features using the Kruskal Wallis test and multivariate logistic regression.Prognostic values were assessed using Cox regression and Kaplan-Meier survival analyses.We further used single-sample gene set enrichment analysis(ssGSEA)to explore correlations between CDC20 expression and immune infiltration levels.Results:CDC20 expression in LUAD tissues was significantly higher than that in normal controls(p<0.001)and showed high diagnostic accuracy(AUC[area under the curve]=0.979).Kaplan-Meier analysis revealed that high CDC20 expression predicted poorer overall survival(OS;HR=1.47,95%CI:1.10–1.97,p=0.009),although no significant association emerged with progression-free interval(p=0.172).ssGSEA indicated a strong positive correlation between CDC20 and T helper 2 cell infiltration(R=0.764,p<0.001),but negative correlations with mast cells(R=−0.469,p<0.001)and eosinophils(R=−0.343,p<0.001).Functional enrichment analyses(Gene ontology/Kyoto Encyclopedia of Genes and Genomes[GO/KEGG])of CDC20-associated genes provided additional mechanistic insights.Conclusions:The significantly elevated expression of CDC20 in LUAD tissues,coupled with its high diagnostic accuracy(AUC=0.979),underscores its potential utility in differentiating LUAD from normal tissue.More importantly,the strong association between high CDC20 expression and poorer overall survival(OS)establishes its independent prognostic value for predicting adverse patient outcomes.Beyond its correlation with clinical parameters,our findings illuminate potential mechanisms underlying CDC20's oncogenic role.The distinct positive correlation with T helper 2(Th2)cell infiltration and negative correlations with mast cells and eosinophils suggest that CDC20 may actively shape an immunosuppressive tumor microenvironment,potentially facilitating tumor immune evasion and progression.Functional enrichment analyses of CDC20-coexpressed genes further support its involvement in key oncogenic pathways,including cell cycle regulation and mitotic processes.Collectively,this study not only validates CDC20 as a valuable prognostic factor but also provides novel mechanistic insights linking its overexpression to altered immune landscapes in LUAD.展开更多
In the heart of Addis Ababa,where tradition meets modern ambition,a gleaming structure of steel and glass is quietly reshaping Africa’s future.The new Africa Centres for Disease Control and Prevention(Africa CDC)Head...In the heart of Addis Ababa,where tradition meets modern ambition,a gleaming structure of steel and glass is quietly reshaping Africa’s future.The new Africa Centres for Disease Control and Prevention(Africa CDC)Headquarters is more than just a building-it’s a bold statement of partnership,progress,and a shared commitment to advancing public health across the continent.展开更多
目的探讨CDC28蛋白激酶调节亚基2(CKS2)对A2780细胞丝足形成的影响及其可能机制。方法采用慢病毒介导的sh RNA敲除A2780细胞的CKS2基因,显微镜下观察细胞丝足的变化;采用细胞划痕实验检测A2780细胞迁移能力的变化;采用real time PCR检测...目的探讨CDC28蛋白激酶调节亚基2(CKS2)对A2780细胞丝足形成的影响及其可能机制。方法采用慢病毒介导的sh RNA敲除A2780细胞的CKS2基因,显微镜下观察细胞丝足的变化;采用细胞划痕实验检测A2780细胞迁移能力的变化;采用real time PCR检测CKS2敲除对CDC42两种剪接变异体(CDC42-V1和CDC42-V2)表达的影响,以及不同卵巢癌标本中CKS2、CDC42-V1和CDC42-V2剪接变异体的表达情况。结果 CKS2表达抑制后,A2780细胞丝足明显减少,细胞迁移能力明显减弱(P<0.05),CDC42-V1 m RNA表达降低,而CDC42-V2 m RNA表达升高(P<0.05)。Real time PCR结果显示,卵巢癌组织标本中CKS2及CDC42-V1的表达高于对应的正常卵巢组织,而CDC42-V2的表达低于对应的正常卵巢组织(P<0.05)。结论 CKS2通过调控CDC42的选择性剪接而影响细胞丝足的形成,进而影响卵巢癌细胞A2780的迁移能力。展开更多
基金funded by the Liaoning Province Science and Technology Plan Joint Project(No.2023JH2/101700140).The funder had no role in the design of the studyin the collection,analyses,or interpretation of data+1 种基金in the writing of the manuscriptor in the decision to publish the results.
文摘Background:Lung adenocarcinoma,the most prevalent lung cancer subtype,is increasingly diagnosed in non-smokers and females.The cell cycle regulator CDC20(Cell Division Cycle 20),a crucial activator of the Anaphase-Promoting Complex/Cyclosome(APC/C),is frequently overexpressed in various cancers,including lung adenocarcinoma,and is implicated in tumorigenesis.Preclinical studies indicate that inhibiting the CDC20-APC/C signaling axis can enhance chemotherapy-induced apoptosis.Analysis of The Cancer Genome Atlas(TCGA)data confirms that elevated CDC20 expression in lung adenocarcinoma is significantly associated with poorer patient prognosis and correlates with immune cell infiltration.These collective findings highlight CDC20 as a promising prognostic biomarker and a potential novel therapeutic target for lung adenocarcinoma.Methods:We collected 539 patients with LUAD and 59 normal controls of clinical data from the Cancer Genome Atlas(TCGA)for bioinformatics analysis to investigate the role of CDC20 in LUAD and address the above questions.We evaluated the association between CDC20 expression and clinicopathological features using the Kruskal Wallis test and multivariate logistic regression.Prognostic values were assessed using Cox regression and Kaplan-Meier survival analyses.We further used single-sample gene set enrichment analysis(ssGSEA)to explore correlations between CDC20 expression and immune infiltration levels.Results:CDC20 expression in LUAD tissues was significantly higher than that in normal controls(p<0.001)and showed high diagnostic accuracy(AUC[area under the curve]=0.979).Kaplan-Meier analysis revealed that high CDC20 expression predicted poorer overall survival(OS;HR=1.47,95%CI:1.10–1.97,p=0.009),although no significant association emerged with progression-free interval(p=0.172).ssGSEA indicated a strong positive correlation between CDC20 and T helper 2 cell infiltration(R=0.764,p<0.001),but negative correlations with mast cells(R=−0.469,p<0.001)and eosinophils(R=−0.343,p<0.001).Functional enrichment analyses(Gene ontology/Kyoto Encyclopedia of Genes and Genomes[GO/KEGG])of CDC20-associated genes provided additional mechanistic insights.Conclusions:The significantly elevated expression of CDC20 in LUAD tissues,coupled with its high diagnostic accuracy(AUC=0.979),underscores its potential utility in differentiating LUAD from normal tissue.More importantly,the strong association between high CDC20 expression and poorer overall survival(OS)establishes its independent prognostic value for predicting adverse patient outcomes.Beyond its correlation with clinical parameters,our findings illuminate potential mechanisms underlying CDC20's oncogenic role.The distinct positive correlation with T helper 2(Th2)cell infiltration and negative correlations with mast cells and eosinophils suggest that CDC20 may actively shape an immunosuppressive tumor microenvironment,potentially facilitating tumor immune evasion and progression.Functional enrichment analyses of CDC20-coexpressed genes further support its involvement in key oncogenic pathways,including cell cycle regulation and mitotic processes.Collectively,this study not only validates CDC20 as a valuable prognostic factor but also provides novel mechanistic insights linking its overexpression to altered immune landscapes in LUAD.
文摘In the heart of Addis Ababa,where tradition meets modern ambition,a gleaming structure of steel and glass is quietly reshaping Africa’s future.The new Africa Centres for Disease Control and Prevention(Africa CDC)Headquarters is more than just a building-it’s a bold statement of partnership,progress,and a shared commitment to advancing public health across the continent.
文摘目的探讨CDC28蛋白激酶调节亚基2(CKS2)对A2780细胞丝足形成的影响及其可能机制。方法采用慢病毒介导的sh RNA敲除A2780细胞的CKS2基因,显微镜下观察细胞丝足的变化;采用细胞划痕实验检测A2780细胞迁移能力的变化;采用real time PCR检测CKS2敲除对CDC42两种剪接变异体(CDC42-V1和CDC42-V2)表达的影响,以及不同卵巢癌标本中CKS2、CDC42-V1和CDC42-V2剪接变异体的表达情况。结果 CKS2表达抑制后,A2780细胞丝足明显减少,细胞迁移能力明显减弱(P<0.05),CDC42-V1 m RNA表达降低,而CDC42-V2 m RNA表达升高(P<0.05)。Real time PCR结果显示,卵巢癌组织标本中CKS2及CDC42-V1的表达高于对应的正常卵巢组织,而CDC42-V2的表达低于对应的正常卵巢组织(P<0.05)。结论 CKS2通过调控CDC42的选择性剪接而影响细胞丝足的形成,进而影响卵巢癌细胞A2780的迁移能力。
