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Logistic Regression Analysis for the Identification of the Metastasis-Associated Signaling Pathways of Osteosarcoma.

International journal of molecular medicine(2018)SCI 3区

Inner Mongolia Univ Nationalities

Cited 7|Views23
Abstract
Osteosarcoma (OS) is the most common histological type of primary bone cancer. The present study was designed to identify the key genes and signaling pathways involved in the metastasis of OS. Microarray data of GSE39055 were downloaded from the Gene Expression Omnibus database, which included 19 OS biopsy specimens before metastasis (control group) and 18 OS biopsy specimens after metastasis (case group). After the differentially expressed genes (DEGs) were identified using the Linear Models for Microarray Analysis package, hierarchical clustering analysis and unsupervised clustering analysis were performed separately, using orange software and the self-organization map method. Based upon the Database for Annotation, Visualization and Integrated Discovery tool and Cytoscape software, enrichment analysis and protein-protein interaction (PPI) network analysis were conducted, respectively. After function deviation scores were calculated for the significantly enriched terms, hierarchical clustering analysis was performed using Cluster 3.0 software. Furthermore, logistic regression analysis was used to identify the terms that were significantly different. Those terms that were significantly different were validated using other independent datasets. There were 840 DEGs in the case group. There were various interactions in the PPI network [including intercellular adhesion molecule-1 (ICAM1), transforming growth factor β1 (TGFB1), TGFB1-platelet-derived growth factor subunit B (PDGFB) and PDGFB-platelet-derived growth factor receptor-β (PDGFRB)]. Regulation of cell migration, nucleotide excision repair, the Wnt signaling pathway and cell migration were identified as the terms that were significantly different. ICAM1, PDGFB, PDGFRB and TGFB1 were identified to be enriched in cell migration and regulation of cell migration. Nucleotide excision repair and the Wnt signaling pathway were the metastasis-associated pathways of OS. In addition, ICAM1, PDGFB, PDGFRB and TGFB1, which were involved in cell migration and regulation of cell migration may affect the metastasis of OS.
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osteosarcoma,differentially expressed genes,protein-protein interaction network,function deviation score
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要点】:本研究采用逻辑回归分析方法识别了与骨肉瘤转移相关的关键基因和信号通路。

方法】:通过线性模型微阵列分析包识别差异表达基因(DEGs),并进行层次聚类和自组织映射的无监督聚类分析,利用数据库注释、可视化和集成发现工具及Cytoscape软件进行富集分析和蛋白质-蛋白质相互作用(PPI)网络分析。

实验】:使用GSE39055微阵列数据集,包含19个转移前骨肉瘤活检样本和18个转移后活检样本,通过逻辑回归分析确定显著差异的术语,并在其他独立数据集上进行验证,发现ICAM1、PDGFB、PDGFRB和TGFB1等基因与细胞迁移和调节细胞迁移相关,而核苷酸切除修复和Wnt信号通路是骨肉瘤转移的关联通路。