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.
The aim of the present study was to identify the important mRNAs, micro (mi)RNAs and long non-coding (lnc)RNAs that are associated with osteosarcoma recurrence. The GSE3905 dataset, which contains two sub-datasets (GSE39040 and GSE39055), was downloaded from the Gene Expression Omnibus (GEO). Prognosis-associated RNAs were identified by performing Cox regression univariate analysis and were subsequently used to construct a competing endogenous (ce)RNA regulatory network for Gene Set Enrichment Analysis (GSEA). Kaplan-Meier survival analysis was used to determine the associations between expression levels and survival prognosis. In addition, another independent miRNA profile, GSE79181, was downloaded from GEO for validation. Among the differentially expressed RNAs, 417 RNAs (5 lncRNAs, 19 miRNAs, and 393 mRNAs) were observed to be associated with prognosis. The GSEA for the ceRNA regulatory network revealed that ‘Mitogen-activated protein kinase (MAPK) signaling pathway’, ‘Chemokine signaling pathway’ and ‘Spliceosome’ were markedly associated with osteosarcoma. In addition, three lncRNAs [long intergenic non-protein coding RNA 28 (LINC00028), LINC00323, and small nucleolar RNA host gene 1 (SNHG1)] and two miRNAs (hsa-miR-124 and hsa-miR-7) regulating three mRNAs [Ras-related protein Rap-1b (RAP1B), activating transcription factor 2 (ATF2) and protein phosphatase Mg2+/Mn2+ dependent 1B (PPM1B)] participated in the MAPK signaling pathway. The Kaplan-Meier survival analysis also demonstrated that samples with lower expression levels of LINC00323 and SNHG1 had better prognosis, and samples with increased expression levels of LINC00028, hsa-miR-124 and hsa-miR-7 had better prognosis. Overexpression of RAP1B, ATF2 and PPM1B was positively associated with osteosarcoma recurrence. The roles of hsa-miR-124 and hsa-miR-7 in osteo-sarcoma recurrence were also validated using GSE79181. Thus, in conclusions, the three lncRNAs (LINC00028, LINC00323 and SNHG1), two miRNAs (hsa-miR-124 and hsa-miR-7) and three mRNAs (RAP1B, ATF2, and PPM1B) were associated with osteosarcoma recurrence.
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