目的基于基因芯片数据分析PHD锌指蛋白19(PHD finger protein 19,PHF19)在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及预后价值。方法下载癌症基因组图谱(The Cancer Genome Atlas,TCGA)肺癌患者数据并分析PHF19在肺癌...目的基于基因芯片数据分析PHD锌指蛋白19(PHD finger protein 19,PHF19)在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及预后价值。方法下载癌症基因组图谱(The Cancer Genome Atlas,TCGA)肺癌患者数据并分析PHF19在肺癌中表达,通过基因表达数据库(Gene Expression Omnibus,GEO)下载数据集GSE30219,GSE50081筛选患者分别纳入训练集和验证集,并分析PHF19表达与肺癌患者性别、年龄、肿瘤临床分期、病理类型与无病生存率(disease free survival,DFS)、总生存率(overall survival,OS)的关系,通过在线数据库对肺癌患者PHF19及共表达相关基因进行基因本体论与京都基因和基因组百科全书(Gene Ontology and Kyoto Encyclopedia of Genes and Genomes,GO-KEGG)富集分析、免疫浸润分析。结果TCGA、GEO数据显示PHF19在肺癌中高表达(P<0.001),PHF19表达与肿瘤分期相关。PHF19低表达组的NSCLC患者较高表达组具有更长的DFS及OS(P均<0.05)。多因素COX回归分析显示PHF19为NSCLC患者独立预后影响因素(P<0.05)。绘制列线图预测肺癌患者的生存率并验证C指数表明模型准确度良好。基因富集分析显示PHF19高表达主要与细胞周期、细胞核、染色质等相关。免疫浸润分析显示PHF19与免疫细胞浸润密切相关。结论PHF19可作为预测NSCLC预后的指标,PHF19高表达是NSCLC不良预后的独立预测因子,可能是其治疗的新的靶点。展开更多
In order to solve the problem of uncertainty and fuzzy information in the process of weapon equipment system selec-tion,a multi-attribute decision-making(MADM)method based on probabilistic hesitant fuzzy set(PHFS)is p...In order to solve the problem of uncertainty and fuzzy information in the process of weapon equipment system selec-tion,a multi-attribute decision-making(MADM)method based on probabilistic hesitant fuzzy set(PHFS)is proposed.Firstly,we introduce the concept of probability and fuzzy entropy to mea-sure the ambiguity,hesitation and uncertainty of probabilistic hesitant fuzzy elements(PHFEs).Sequentially,the expert trust network is constructed,and the importance of each expert in the network can be obtained by calculating the cumulative trust value under multiple trust propagation paths,so as to obtain the expert weight vector.Finally,we put forward an MADM method combining the probabilistic hesitant fuzzy entropy and grey rela-tion analysis(GRA)model,and an illustrative case is employed to prove the feasibility and effectiveness of the method when solving the weapon system selection decision-making problem.展开更多
目的探讨PHF2在乳腺癌细胞和组织中的表达及其与乳腺癌临床病理特征、预后的关系。方法采用q RT-PCR法检测乳腺癌及正常乳腺上皮细胞株(n=7)及配对的癌旁组织(n=30)中PHF2 m RNA的表达水平;应用Western blot法检测乳腺癌细胞株中PHF2蛋...目的探讨PHF2在乳腺癌细胞和组织中的表达及其与乳腺癌临床病理特征、预后的关系。方法采用q RT-PCR法检测乳腺癌及正常乳腺上皮细胞株(n=7)及配对的癌旁组织(n=30)中PHF2 m RNA的表达水平;应用Western blot法检测乳腺癌细胞株中PHF2蛋白的表达水平,免疫组化法检测乳腺癌组织(n=50)和癌旁组织(n=15)中PHF2蛋白的表达,分析PHF2表达与乳腺癌临床病理特征的关系及预后的关系。结果与正常人乳腺上皮细胞相比,PHF2 m RNA和蛋白在乳腺癌细胞株中表达下调(P<0.01);与癌旁组织相比,PHF2 m RNA在90%(27/30)的乳腺癌组织中表达下调(P<0.05);免疫组化结果显示:在70%(35/50)的乳腺癌组织中PHF2蛋白表达下调(P<0.05);PHF2表达下调与乳腺癌患者的淋巴结转移、ER阴性及预后密切相关(P<0.05)。结论 PHF2在乳腺癌中表达下调,可以作为乳腺癌预后判断的指标之一,有望成为乳腺癌治疗的新靶点。展开更多
Dimethylation of histone H3 lysine 9 （H3K9me2） is an important epigenetic mark associated with transcription repression. Here, we identified PHF8, a JmjC-domain-containing protein, as a histone demethylase specific ...Dimethylation of histone H3 lysine 9 （H3K9me2） is an important epigenetic mark associated with transcription repression. Here, we identified PHF8, a JmjC-domain-containing protein, as a histone demethylase specific for this repressing mark. Recombinant full-length wild type protein could remove methylation from H3K9me2, but mutation of a conserved histidine to alanine H247A abolished the demethylase activity. Overexpressed exogenous PHF8 was colocalized with B23 staining. Endogenous PHF8 was also colocalized with B23 and fibrillarin, two well-established nucleolus proteins, suggesting that PHF8 is localized in the nucleolus and may regulate rRNA transcription. Indeed, PHF8 bound to the promoter region of the rDNA gene. Knockdown of PHF8 reduced the expression of rRNA, and overexpression of the gene resulted in upregulation of rRNA transcript. Concomitantly, H3K9me2 level was elevated in the promoter region of the rDNA gene in PHF8 knockdown cells and reduced significantly when the wild type but not the catalytically inactive H247A mutant PHF8 was overexpressed. Thus, our study identified a histone demethylase for H3K9me2 that regulates rRNA transcription.展开更多
文摘目的基于基因芯片数据分析PHD锌指蛋白19(PHD finger protein 19,PHF19)在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及预后价值。方法下载癌症基因组图谱(The Cancer Genome Atlas,TCGA)肺癌患者数据并分析PHF19在肺癌中表达,通过基因表达数据库(Gene Expression Omnibus,GEO)下载数据集GSE30219,GSE50081筛选患者分别纳入训练集和验证集,并分析PHF19表达与肺癌患者性别、年龄、肿瘤临床分期、病理类型与无病生存率(disease free survival,DFS)、总生存率(overall survival,OS)的关系,通过在线数据库对肺癌患者PHF19及共表达相关基因进行基因本体论与京都基因和基因组百科全书(Gene Ontology and Kyoto Encyclopedia of Genes and Genomes,GO-KEGG)富集分析、免疫浸润分析。结果TCGA、GEO数据显示PHF19在肺癌中高表达(P<0.001),PHF19表达与肿瘤分期相关。PHF19低表达组的NSCLC患者较高表达组具有更长的DFS及OS(P均<0.05)。多因素COX回归分析显示PHF19为NSCLC患者独立预后影响因素(P<0.05)。绘制列线图预测肺癌患者的生存率并验证C指数表明模型准确度良好。基因富集分析显示PHF19高表达主要与细胞周期、细胞核、染色质等相关。免疫浸润分析显示PHF19与免疫细胞浸润密切相关。结论PHF19可作为预测NSCLC预后的指标,PHF19高表达是NSCLC不良预后的独立预测因子,可能是其治疗的新的靶点。
基金supported by the National Natural Science Foundation of China(71901214).
文摘In order to solve the problem of uncertainty and fuzzy information in the process of weapon equipment system selec-tion,a multi-attribute decision-making(MADM)method based on probabilistic hesitant fuzzy set(PHFS)is proposed.Firstly,we introduce the concept of probability and fuzzy entropy to mea-sure the ambiguity,hesitation and uncertainty of probabilistic hesitant fuzzy elements(PHFEs).Sequentially,the expert trust network is constructed,and the importance of each expert in the network can be obtained by calculating the cumulative trust value under multiple trust propagation paths,so as to obtain the expert weight vector.Finally,we put forward an MADM method combining the probabilistic hesitant fuzzy entropy and grey rela-tion analysis(GRA)model,and an illustrative case is employed to prove the feasibility and effectiveness of the method when solving the weapon system selection decision-making problem.
文摘目的探讨PHF2在乳腺癌细胞和组织中的表达及其与乳腺癌临床病理特征、预后的关系。方法采用q RT-PCR法检测乳腺癌及正常乳腺上皮细胞株(n=7)及配对的癌旁组织(n=30)中PHF2 m RNA的表达水平;应用Western blot法检测乳腺癌细胞株中PHF2蛋白的表达水平,免疫组化法检测乳腺癌组织(n=50)和癌旁组织(n=15)中PHF2蛋白的表达,分析PHF2表达与乳腺癌临床病理特征的关系及预后的关系。结果与正常人乳腺上皮细胞相比,PHF2 m RNA和蛋白在乳腺癌细胞株中表达下调(P<0.01);与癌旁组织相比,PHF2 m RNA在90%(27/30)的乳腺癌组织中表达下调(P<0.05);免疫组化结果显示:在70%(35/50)的乳腺癌组织中PHF2蛋白表达下调(P<0.05);PHF2表达下调与乳腺癌患者的淋巴结转移、ER阴性及预后密切相关(P<0.05)。结论 PHF2在乳腺癌中表达下调,可以作为乳腺癌预后判断的指标之一,有望成为乳腺癌治疗的新靶点。
基金Acknowledgments We thank the cell biology core facility for confocal study. The PHF8 antibody was kindly provided by Dr Jiemin Wong （East China Normal University）. This work was supported by the National Basic Research Program of China （2007CB947900, 2010CB529705, 2007CB947100）, the Chinese Academy of Sci- ences （KSCX2-YW-R-04, KSCX2-YW-R-I 11）, the National Natural Science Foundation of China （30870538, 90919026）, Postdoctoral fellowship （20090460670）, and the Council of Shanghai Municipal Government for Science and Technology.
文摘Dimethylation of histone H3 lysine 9 （H3K9me2） is an important epigenetic mark associated with transcription repression. Here, we identified PHF8, a JmjC-domain-containing protein, as a histone demethylase specific for this repressing mark. Recombinant full-length wild type protein could remove methylation from H3K9me2, but mutation of a conserved histidine to alanine H247A abolished the demethylase activity. Overexpressed exogenous PHF8 was colocalized with B23 staining. Endogenous PHF8 was also colocalized with B23 and fibrillarin, two well-established nucleolus proteins, suggesting that PHF8 is localized in the nucleolus and may regulate rRNA transcription. Indeed, PHF8 bound to the promoter region of the rDNA gene. Knockdown of PHF8 reduced the expression of rRNA, and overexpression of the gene resulted in upregulation of rRNA transcript. Concomitantly, H3K9me2 level was elevated in the promoter region of the rDNA gene in PHF8 knockdown cells and reduced significantly when the wild type but not the catalytically inactive H247A mutant PHF8 was overexpressed. Thus, our study identified a histone demethylase for H3K9me2 that regulates rRNA transcription.
