Department of Orthopedics, Affiliated Hospital of Inner Mongolia University for The Nationalities, Tongliao, Inner Mongolia 028007, P.R. China.
Department of Orthopaedics, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, P.R. China.
Int J Mol Med. 2018 Mar;41(3):1233-1244. doi: 10.3892/ijmm.2018.3360. Epub 2018 Jan 2.
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.
骨肉瘤(OS)是原发性骨癌中最常见的组织学类型。本研究旨在鉴定骨肉瘤转移中涉及的关键基因和信号通路。从基因表达综合数据库中下载了 GSE39055 的微阵列数据,其中包括 19 例转移前(对照组)和 18 例转移后(病例组)骨肉瘤活检标本。使用线性模型微阵列分析程序包鉴定差异表达基因(DEGs)后,分别使用橙色软件和自组织映射方法进行层次聚类分析和无监督聚类分析。基于数据库注释、可视化和综合发现工具以及 Cytoscape 软件,分别进行了富集分析和蛋白质-蛋白质相互作用(PPI)网络分析。计算显著富集术语的功能偏差得分后,使用 Cluster 3.0 软件进行层次聚类分析。此外,使用逻辑回归分析识别差异显著的术语。使用其他独立数据集验证差异显著的术语。病例组中有 840 个 DEGs。在 PPI 网络中存在各种相互作用[包括细胞间黏附分子-1(ICAM1)、转化生长因子β1(TGFB1)、TGFB1-血小板衍生生长因子亚基 B(PDGFB)和 PDGFB-血小板衍生生长因子受体-β(PDGFRB)]。鉴定出细胞迁移、核苷酸切除修复、Wnt 信号通路和细胞迁移的调控是差异显著的术语。ICAM1、PDGFB、PDGFRB 和 TGFB1 被鉴定为富集在细胞迁移和细胞迁移的调控中。核苷酸切除修复和 Wnt 信号通路是骨肉瘤转移的相关途径。此外,参与细胞迁移和细胞迁移调控的 ICAM1、PDGFB、PDGFRB 和 TGFB1 可能影响骨肉瘤的转移。