Identification of characteristic gene modules of osteosarcoma using bioinformatics analysis indicates the possible molecular pathogenesis

Abstract

The aim of the present study was to investigate the possible pathogenesis of osteosarcoma using bioinformatics analysis to examine gene-gene interactions. A total of three datasets associated with osteosarcoma were downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) were identified using the significance analysis of microarrays method, which then were subjected to the Human Protein Reference Database to identify the protein-protein interaction (PPI) pairs and to construct a PPI network of the DEGs. Subsequent multilevel community analysis was applied to mine the modules in the network, followed by screening of the differential expression module using the GlobalAncova package. The genes in the differential expression modules were verified in the valid datasets. The verified genes underwent functional and pathway enrichment analysis. A total of 616 DEGs were selected to construct the PPI network, which included 5,808 osteosarcoma-specific interaction pairs and 8,012 normal-specific pairs. Tumor protein p53 (TP53), mitogen-activated protein kinase 1 (MAPK1) and estrogen receptor 1 (ESR1) were identified the most important osteosarcoma-associated genes, with the highest levels of topological properties. Neurogenic locus notch homolog protein 3 (NOTCH3) and caspase 1 (CASP1) were identified as the osteosarcoma-specific interaction pairs. Among all 23 mined modules, three were identified as differential expression modules, which were verified in the other two datasets. The genes in these modules were predominantly enriched in the FGFR, MAPK and Notch signaling pathways. Therefore, TP53, MAPK1, ESR1, NOTCH3 and CASP1 may be important in the development of osteosarcoma, and provides valuable clues to investigate the pathogenesis of osteosarcoma using the three differential expression modules.

Systematic screening for potential therapeutic targets in osteosarcoma through a kinome-wide CRISPR-Cas9 library

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Expression of miR‑542‑3p in osteosarcoma with miRNA microarray data, and its potential signaling pathways

“…In a bioinformatics study, Li et al (24) predicted that the MAPK1 gene is the most important gene associated with OS. Their findings were consistent with the results of the present study; however, the role of this gene in OS is yet to be verified experimentally.…”

Circ0085539 Promotes Osteosarcoma Progression by Suppressing miR-526b-5p and PHLDA1 Axis

“…Extensive studies have been conducted to discover potential therapeutic targets for osteosarcoma ( 25 , 26 ). These promising targets cover a wide spectrum of RNAs including circular RNAs, lncRNAs, miRNAs, and mRNAs.…”