Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively...Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The purpose of this study was to clarify the correlation between PAEP expression level and bladder cancer. Methods: In the TCGA database, we obtained clinical and RNA sequencing data of 431 BLCA patients, including 412 BLCA tissues and 19 normal bladder tissues in the study. Analyses of bioinformatics were conducted in this study to determine the role of PAEP in bladder cancer. A quantitative real-time PCR method was used to quantitate the gene expression profile. Additionally, the effect of PAEP on tumor immune infiltration and prognosis was analyzed. Results: PAEP was a poor prognostic biomarker of bladder cancer because it was significantly upregulated. bladder cancer patients with higher PAEP expression had poor outcomes. An AUC of 0.780 was calculated from the area under the ROC curve. PAEP was associated with T stage, pathologic stage, Histologic grade and Subtype of bladder cancer patients, and served as an independent predictor of overall survival in bladder cancer patients. Functional enrichment analysis revealed PAEP was obviously enriched in pathways connected with carcinogenesis and immunosuppression. The expression of PAEP was significantly associated with tumor immune cells and immune checkpoints according to ssGSEA and Spearman correlation analysis. Conclusions: In this study, we screened and detected a mRNA, PAEP is a prognostic and immune-related biomarker in BLCA, which may contribute to the early diagnosis and treatment of BLCA.展开更多
为探究OSBPL11、PAEP、ALDH1A2基因多态性与胸椎数之间的关联性,筛选胸椎数相关重要分子标记,本研究利用Sequenom Mass ARRAY?SNP技术检测苏尼特羊和小尾寒羊与胸椎数相关的重要候选基因OSBPL11、PAEP、ALDH1A2的单核苷酸多态性(SNPs)位...为探究OSBPL11、PAEP、ALDH1A2基因多态性与胸椎数之间的关联性,筛选胸椎数相关重要分子标记,本研究利用Sequenom Mass ARRAY?SNP技术检测苏尼特羊和小尾寒羊与胸椎数相关的重要候选基因OSBPL11、PAEP、ALDH1A2的单核苷酸多态性(SNPs)位点,开展群体遗传学分析,并与胸椎数进行关联分析。结果显示,小尾寒羊和苏尼特羊群体中OSBPL11基因g.188064535A>G位点含有AA、AG和GG 3种基因型,PAEP基因g.3541777A>G位点含有AA、AG和GG3种基因型,ALDH1A2基因g.49249275G>A含有GG和AG 2种基因型。OSBPL11基因g.188064535A>G位点中小尾寒羊和苏尼特羊均为低度多态(PIC<0.25);PAEP基因g.3541777A>G位点中小尾寒羊和苏尼特羊均为中度多态(0.25A位点中小尾寒羊和苏尼特羊均为低度多态(PIC<0.25)。小尾寒羊和苏尼特羊3个候选基因的SNPs均处于哈代温伯格平衡状态(P>0.05)。关联分析结果表明,在苏尼特羊中ALDH1A2基因g.49249275G>A位点野生型(GG)的胸椎数显著低于杂合型(AG),其他位点在小尾寒羊和苏尼特羊中与胸椎数均没有显著关系。综上所述,ALDH1A2基因g.49249275G>A位点可作为潜在的绵羊多胸椎数分子标记。本研究结果为提高绵羊胸椎数、改良绵羊生长发育提供了理论基础。展开更多
Objective This study aims to gain further the potential mechanisms of HIF-2αin tumor progression and tumorigenesis.Methods Mined The Cancer Genome Atlas(TCGA)dataset.In total,421 participants were enrolled in the TCG...Objective This study aims to gain further the potential mechanisms of HIF-2αin tumor progression and tumorigenesis.Methods Mined The Cancer Genome Atlas(TCGA)dataset.In total,421 participants were enrolled in the TCGAHepatocellular Carcinoma(HCC)study,comprising 371 patients with cancer and 50 healthy controls.From the 371 tumor samples,three samples containing the missense mutation of the HIF-2αgene were compared with 368 wild-type samples to identify differentially expressed genes(DEGs).Results After filtering,univariate Cox regression and multivariate Cox regression analyses showed that the differentially expressed genes(DEGs)progestagen-associated endometrial protein(PAEP)PNLIPRP2,MIR147B,and pregnancy zone protein(PZP)were significantly correlated with the survival times of patients with HCC.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed using the Database for Annotation,Visualization,and Integrated Discovery(DAVID)v6.8 database to detect the functional annotation of these four DEGs as well as hub genes obtained from protein-protein interaction(PPI)network analysis using the STRING v10 database.Our analysis focused on the PAEP and PZP genes,whose protein expressions were downregulated in samples with HIF-2αmissense mutation.The hub genes of PAEP and PZP were identified using PPI network analysis.Subsequent Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed that PAEP and its hub genes were highly enriched in the TGF-βpathway,which is consistent with the analysis of PZP.Conclusion Our study proved that the missense mutation of HIF-2αinduces the upregulation of PAEP,which is positively related to the poor prognosis of patients with HCC,as it may upregulate the TGF-βpathway.In contrast,PZP downregulation showed the opposite phenomenon,as it may downregulate the TGF-βpathway.展开更多
文摘Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The purpose of this study was to clarify the correlation between PAEP expression level and bladder cancer. Methods: In the TCGA database, we obtained clinical and RNA sequencing data of 431 BLCA patients, including 412 BLCA tissues and 19 normal bladder tissues in the study. Analyses of bioinformatics were conducted in this study to determine the role of PAEP in bladder cancer. A quantitative real-time PCR method was used to quantitate the gene expression profile. Additionally, the effect of PAEP on tumor immune infiltration and prognosis was analyzed. Results: PAEP was a poor prognostic biomarker of bladder cancer because it was significantly upregulated. bladder cancer patients with higher PAEP expression had poor outcomes. An AUC of 0.780 was calculated from the area under the ROC curve. PAEP was associated with T stage, pathologic stage, Histologic grade and Subtype of bladder cancer patients, and served as an independent predictor of overall survival in bladder cancer patients. Functional enrichment analysis revealed PAEP was obviously enriched in pathways connected with carcinogenesis and immunosuppression. The expression of PAEP was significantly associated with tumor immune cells and immune checkpoints according to ssGSEA and Spearman correlation analysis. Conclusions: In this study, we screened and detected a mRNA, PAEP is a prognostic and immune-related biomarker in BLCA, which may contribute to the early diagnosis and treatment of BLCA.
文摘为探究OSBPL11、PAEP、ALDH1A2基因多态性与胸椎数之间的关联性,筛选胸椎数相关重要分子标记,本研究利用Sequenom Mass ARRAY?SNP技术检测苏尼特羊和小尾寒羊与胸椎数相关的重要候选基因OSBPL11、PAEP、ALDH1A2的单核苷酸多态性(SNPs)位点,开展群体遗传学分析,并与胸椎数进行关联分析。结果显示,小尾寒羊和苏尼特羊群体中OSBPL11基因g.188064535A>G位点含有AA、AG和GG 3种基因型,PAEP基因g.3541777A>G位点含有AA、AG和GG3种基因型,ALDH1A2基因g.49249275G>A含有GG和AG 2种基因型。OSBPL11基因g.188064535A>G位点中小尾寒羊和苏尼特羊均为低度多态(PIC<0.25);PAEP基因g.3541777A>G位点中小尾寒羊和苏尼特羊均为中度多态(0.25A位点中小尾寒羊和苏尼特羊均为低度多态(PIC<0.25)。小尾寒羊和苏尼特羊3个候选基因的SNPs均处于哈代温伯格平衡状态(P>0.05)。关联分析结果表明,在苏尼特羊中ALDH1A2基因g.49249275G>A位点野生型(GG)的胸椎数显著低于杂合型(AG),其他位点在小尾寒羊和苏尼特羊中与胸椎数均没有显著关系。综上所述,ALDH1A2基因g.49249275G>A位点可作为潜在的绵羊多胸椎数分子标记。本研究结果为提高绵羊胸椎数、改良绵羊生长发育提供了理论基础。
文摘Objective This study aims to gain further the potential mechanisms of HIF-2αin tumor progression and tumorigenesis.Methods Mined The Cancer Genome Atlas(TCGA)dataset.In total,421 participants were enrolled in the TCGAHepatocellular Carcinoma(HCC)study,comprising 371 patients with cancer and 50 healthy controls.From the 371 tumor samples,three samples containing the missense mutation of the HIF-2αgene were compared with 368 wild-type samples to identify differentially expressed genes(DEGs).Results After filtering,univariate Cox regression and multivariate Cox regression analyses showed that the differentially expressed genes(DEGs)progestagen-associated endometrial protein(PAEP)PNLIPRP2,MIR147B,and pregnancy zone protein(PZP)were significantly correlated with the survival times of patients with HCC.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed using the Database for Annotation,Visualization,and Integrated Discovery(DAVID)v6.8 database to detect the functional annotation of these four DEGs as well as hub genes obtained from protein-protein interaction(PPI)network analysis using the STRING v10 database.Our analysis focused on the PAEP and PZP genes,whose protein expressions were downregulated in samples with HIF-2αmissense mutation.The hub genes of PAEP and PZP were identified using PPI network analysis.Subsequent Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed that PAEP and its hub genes were highly enriched in the TGF-βpathway,which is consistent with the analysis of PZP.Conclusion Our study proved that the missense mutation of HIF-2αinduces the upregulation of PAEP,which is positively related to the poor prognosis of patients with HCC,as it may upregulate the TGF-βpathway.In contrast,PZP downregulation showed the opposite phenomenon,as it may downregulate the TGF-βpathway.
