Dataset Information

Identification of critical genes and gene interaction networks that mediate osteosarcoma metastasis to the lungs.

ABSTRACT: Osteosarcoma (OS) is the most commonly diagnosed bone tumor in young adults under the age of 20. Metastasis is considered an important factor underlying cancer-associated morbidity and mortality, and, as a result, the survival rate of patients with metastatic OS is low. In spite of this, the mechanisms underlying metastasis in OS are currently not well understood. The present study compared gene expression levels between five non-metastatic and four metastatic OS tumor samples, using an Affymetrix microarray. A total of 282 genes were differentially expressed in the metastatic samples, as compared with the non-metastatic samples. Of these differentially expressed genes (DEGs), 212 were upregulated and 70 were downregulated. The following DEGs were associated with metastasis: Homeobox only protein; lysosomal-associated membrane protein-3; chemokine (C-C motif) ligand-18; carcinoembryonic antigen-related cell adhesion molecule-6; keratin-19; prostaglandin-endoperoxide synthase-2; clusterin; and nucleoside diphosphate kinase-1. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses were conducted, which identified 529 biological processes (P<0.01) and 10 KEGG pathways (P<0.05) that were significantly over-represented in the metastatic samples, as compared with the non-metastatic samples. Interaction networks for the DEGs were constructed using the corresponding GO terms and KEGG pathways, and these identified numerous genes that may contribute to OS metastasis. Among the enriched biological processes, four DEGs were consistently over-represented: Jun proto-oncogene, caveolin-1, nuclear factor-?B-inhibitor-? and integrin alpha-4; thus suggesting that they may have key roles in OS metastasis, and may be considered potential therapeutic targets in the treatment of patients with OS.

SUBMITTER: Liu K

PROVIDER: S-EPMC4665845 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Identification of critical genes and gene interaction networks that mediate osteosarcoma metastasis to the lungs.

Liu Kegui K He Qunhui Q Liao Guangjun G Han Jian J

Experimental and therapeutic medicine 20150923 5

Osteosarcoma (OS) is the most commonly diagnosed bone tumor in young adults under the age of 20. Metastasis is considered an important factor underlying cancer-associated morbidity and mortality, and, as a result, the survival rate of patients with metastatic OS is low. In spite of this, the mechanisms underlying metastasis in OS are currently not well understood. The present study compared gene expression levels between five non-metastatic and four metastatic OS tumor samples, using an Affymetr ...[more]

PMID: 26640552

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Project description: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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Dataset Information

Identification of critical genes and gene interaction networks that mediate osteosarcoma metastasis to the lungs.

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Identification of critical genes and gene interaction networks that mediate osteosarcoma metastasis to the lungs.

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