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• Research Paper Volume 11, Issue 14 pp 5158-5172

  The diagnostic and prognostic role of RhoA in hepatocellular carcinoma

  Relevance score: 8.476041

  Yi Bai, Fucun Xie, Fei Miao, Junyu Long, Shan Huang, Hanchun Huang, Jianzhen Lin, Dongxu Wang, Xu Yang, Jin Bian, Jinzhu Mao, Xi Wang, Yilei Mao, Xinting Sang, Haitao Zhao

  Keywords: RhoA, hepatocellular carcinoma, expression level, prognostic biomarker, diagnostic biomarker, aging, age-related diseases

  Published in Aging on July 22, 2019

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  The aim of this study was to investigate the expression level of Ras homolog gene family, member A (RhoA) in patients with hepatocellular carcinoma (HCC) and to investigate the prognostic and diagnostic value of RhoA. Data mining from various data bases and wet experiments on samples from Peking Union Medical College Hospital showed that RhoA mRNA and protein expression were significantly higher in the HCC tissues than in the normal tissues. Higher expression at both the mRNA and protein levels was associated with a poorer prognosis. High sensitivity (92.5%) and specificity (90.0%) were observed in the diagnostic model based on protein level rather than mRNA level. RhoA expression was modulated by genetic amplification. The lysosome, pathogenic Escherichia coli infection, purine metabolism and pyrimidine metabolism pathways were mainly enriched in the high RhoA level group, while the hedgehog signaling, linoleic acid metabolism, olfactory transduction and taste transduction pathways were enriched in the low RhoA level group. RhoA is commonly upregulated in HCC tissues, and its expression at both the mRNA and protein levels is associated with poor prognosis. Notably, RhoA protein levels serve as a diagnostic biomarker for HCC.

  

  Gene and protein expression profiles of RhoA in tissue samples and cancer cell lines.RhoA mRNA expression (A) data from the GTEx dataset in the Human Protein Atlas) and protein expression (B) data from the Human Protein Atlas) in normal human tissues. RhoA gene expression in common human tumor tissues (C) data from the TCGA dataset in the Human Protein Atlas). Comparison of RhoA mRNA expression between hepatocellular carcinoma tissues and normal liver tissues, including normal TCGA and GTEx data (D) data from GEPIA). RhoA protein expression overview in human tumor tissues (E) data from the TCGA CAB005052 dataset in the Human Protein Atlas) and representative immunohistochemistry (IHC) images (F) pictures from the Human Protein Atlas) with RhoA antibody (1:25, Cat#1600-1, Abcam, Cambridge, UK). RhoA mRNA expression in human cancer cell lines (G, data from RNA cell line category in the Human Protein Atlas).

  
  
  

  

  RhoA expression level as an independent prognostic factor in HCC. The high expression level of RhoA suggests poor prognosis based on the TCGA training set (A), and the optimal cutoff point was calculated via the X-tile method (B). High RhoA expression levels were also unfavorable in two GEO validation sets (C, GSE10186; D, GSE54236). Univariate and multivariate Cox regression analyses of clinical indicators and RhoA levels related to prognosis: red bars represent prognostic factors, and blue bars represent nonprognostic factors (E).

  
  
  

  

  RhoA mRNA expression in different groups of patients and differential expression verification. Relative expression of RhoA in males and females (A), stage I-II and stage III-IV (B), and grade 1–2 and grade 3–4 (C) from TCGA data. The relative RhoA expression in ten pairs of normal tissues and HCC tissues from Peking Union Medical College Hospital identified through real-time quantitative polymerase chain reaction (D). The representative immunohistochemistry images of HCC tissue (lower right) and adjacent normal tissue (upper right): The red squares shown in the figure represents the enlarged area. (E).

  
  
  

  

  Diagnostic model of RhoA protein expression in liver cancer patients. The staining intensities of RhoA via immunohistochemistry chips from PUMCH patient samples (A). Kaplan-Meier curves of overall survival (B) of liver cancer patients with high RhoA protein expression levels (3+) and low RhoA protein expression levels (0–2+). Diagram (C), sensitivity and specificity validation (D) and receiver operating characteristic curve (E) of the diagnostic model according to RhoA immunohistochemistry level.

  
  
  

  

  RhoA dysregulation and related KEGG analysis. Multiomic data of RhoA in liver cancer tissues are displayed in a heatmap (A). The correlation between RhoA gene expression level and copy number variation level (B) or DNA methylation level (C) were determined by regression analysis. The top 4 Kyoto Encyclopedia of Genes and Genomes pasthways identified via gene set enrichment analysis of tissues with high and low Rho expression levels (D).

  
  
  

• Research Paper Volume 8, Issue 11 pp 2734-2746

  Characterization of variations in IL23A and IL23R genes: possible roles in multiple sclerosis and other neuroinflammatory demyelinating diseases

  Relevance score: 10.803041

  Fei-Feng Li, Xi-Dong Zhu, Peng Yan, Mei-Hua Jin, Hui Yue, Qiong Zhang, Jin Fu, Shu-Lin Liu

  Keywords: multiple sclerosis, IDD, interleukin-23A, gene expression level, SNP

  Published in Aging on November 26, 2016

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  Multiple sclerosis is among the most serious inflammatory demyelinating diseases (IDD). Interleukin-23A (IL23A) regulates and coordinates the activities of immune cells by interacting with its receptor IL23R and plays key roles in the pathogenesis of immune inflammatory diseases. IDD, deemed to be a kind of autoimmune diseases, may involve IL23A in the pathogenesis. The aim of this work was to validate the hypothesized involvement of IL-23A and its receptor in IDD. We sequenced the IL-23A and IL-23R genes for 206 Chinese Han IDD patients and evaluated SNPs within or near those genes. The serum levels of IL23A in IDD participants were analyzed using ELISA. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). The Hardy-Weinberg equilibrium test of the population was carried out using online software OEGE. Three variants rs2066808, rs2371494, rs11575248 in IL-23A gene and one variant rs1884444 in IL-23R gene were demonstrated to be associated with the risk of MS or other IDD diseases, and the expression level of serum IL-23A in the MS patients was also altered. We conclude that variants in IL-23A and IL-23R genes were associated with the risk of MS or other IDD diseases.

  

  LD analysis of the variants in the IL23A gene region, and the LD plots were generated using the Haploview software v4.2. (A) Data analysis between IDD patients and controls from the present study. (B) Data from the HapMap CHB. The data from the HapMap CHB and this work were very similar.

  
  
  

  

  The serum levels of IL23A in IDD and normal groups were detected by ELISA. (A) The expression levels of IL23A in the MS patients were higher than that in the control group (two asterisk); and when both the IL-23A and IL-23R genes were altered, the serum levels of IL23A were higher than those in the groups in which neither the IL-23A nor the IL-23R gene was altered or only one of them was altered. (B) The expression levels of IL23A in the RIS patients were higher than those in the control group (two asterisks); however there was no difference between the three groups that had the IL-23A and IL-23R genes both altered, only one altered or neither altered. “WW” means neither the IL-23A nor the IL-23R gene was altered; “MM” means the IL-23A and IL-23R genes were both altered; “Homozygous variant” means the homozygous variant G/G of the rs1884444 variant in the IL-23R gene.

  
  
  

  

  Schematic diagrams of the variants. (A) the IL-23A gene variants rs2066808, rs2371494 and rs11575248; (B): the IL-23R gene variant rs1884444.

  
  
  

• Research Paper pp undefined-undefined

  Combined analysis of expression, prognosis and immune infiltration of GINS family genes in human sarcoma

  Relevance score: 12.193643

  Kexin Zhang, Jian Zhou, Tong Wu, Qunyan Tian, Tang Liu, Wanchun Wang, Hua Zhong, Ziyuan Chen, Xungang Xiao, Gen Wu

  Keywords: sarcoma, prognosis, expression level, GINS

  Published in Aging on Invalid Date

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  Objective: This study was undertaken to explore the expression and prognostic value of GINS family in human sarcoma, as well as the association between the expression levels of the GINS family and sarcoma immune infiltration.

  Results: We discovered that the mRNA expression levels of GINS1, GINS2, GINS3, and GINS4 were all higher in the majority of tumor tissues than in normal samples, of course, including sarcoma. Through the CCLE, all the four members expression were observed in high levels in sarcoma cell lines. In Gene Expression Profiling Analysis (GEPIA) and Kaplan-Meier Plotter, our results indicated that the poor overall survival (OS), disease-free survival (DFS) and relapse free survival (RFS) were tightly associated with the increased expression of GINS genes. In TIMER database, we found that highly expressed GINS was significantly correlated with the low infiltration level of CD4+ T cell and macrophage.

  Conclusions: The four GINS family members were all the prognostic biomarkers for the prognosis of human sarcoma and can reduce the level of immune cell infiltration in the sarcoma microenvironment.

  Methods: In terms of the expression levels of mRNA for GINS family members, a particular contrast in various cancers, especially human sarcoma, was conducted through ONCOMINE and GEPIA and CCLE databases. Kaplan-Meier Plotter was used to identify the prognostic value of GINS family in sarcoma. The relationship between the expression level of GINS and the infiltration of immune cells was analyzed in TIMER database.