Identification of critical genes associated with human osteosarcoma metastasis based on integrated gene expression profiling

Fan,Hongwu; Lu,Shan; Wang,Shengqun; Zhang,Shanyong

doi:10.3892/mmr.2019.10323

Identification of critical genes associated with human osteosarcoma metastasis based on integrated gene expression profiling

Authors:
- Hongwu Fan
- Shan Lu
- Shengqun Wang
- Shanyong Zhang
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Affiliations: Department of Orthopedics, China Japan Union Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Anesthesiology, China Japan Union Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Spinal Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
Published online on: June 3, 2019 https://doi.org/10.3892/mmr.2019.10323
Pages: 915-930
Copyright: © Fan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteosarcoma is the most common type of malignant bone cancer, which often affects teenagers and young adults. The present study aimed to screen for critical genes and microRNAs (miRNAs/miRs) involved in osteosarcoma. A total of four microarray datasets (accession numbers GSE32981, GSE21257, GSE14827 and GSE14359) were downloaded from the Gene Expression Omnibus database. Following data preprocessing, module analysis was performed to identify the stable modules using the weighted gene co‑expression network analysis (WGCNA) package. The differentially expressed genes (DEGs) between metastatic samples and non‑metastatic samples were screened, followed by gene co‑expression network construction, and Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Subsequently, prognosis‑associated genes were screened and a miRNA‑target gene regulatory network was constructed. Finally, the data for critical genes were validated. WGCNA analysis identified six modules; blue and yellow modules were significantly positively associated with osteosarcoma metastasis. A total of 1,613 DEGs were screened between primary tissue samples and metastatic samples. Following comparison of the genes in the two (blue and yellow) modules, a total of 166 DEGs were identified (metastatic samples vs. non‑metastatic samples). Functional enrichment analysis demonstrated that these DEGs were mainly involved in ‘defense response’, ‘p53 signaling pathway’ and ‘lysosome’. By utilizing the clinical information in GSE21257, 10 critical genes associated with osteosarcoma prognosis were obtained, including CTP synthase 2 (CTPS2), tumor protein p53 inducible protein 3 (TP53I3) and solute carrier family 1 member 1 (SLC1A1). In addition, hsa‑miR‑422a and hsa‑miR‑194 were highlighted in the miRNA‑target gene network. Finally, matrix metallopeptidase 3 (MMP3) and vascular endothelial growth factor B (VEGFB) were predicted as critical genes in osteosarcoma metastasis. CTPS2, TP53I3 and SLC1A1 may serve major roles in osteosarcoma development, and hsa‑miR‑422a, hsa‑miR‑194, MMP3 and VEGFB may be associated with osteosarcoma metastasis.

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