RESUMEN
Objective To screen the potential key genes of osteosarcoma by bioinformatics methods and analyze their immune infiltration patterns. Methods The gene expression profiles GSE16088 and GSE12865 associated with osteosarcoma were obtained from the Gene Expression Omnibus(GEO),and the differentially expressed genes(DEGs)related to osteosarcoma were screened by bioinformatics tools.Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and analysis of immune cell infiltration were then carried out for the DEGs.The potential Hub genes of osteosarcoma were identified by protein-protein interaction network,and the expression of Hub genes in osteosarcoma and normal tissue samples was verified via the Cancer Genome Atlas(TCGA). Results A total of 108 DEGs were screened out.GO annotation and KEGG pathway enrichment revealed that the DEGs were mainly involved in integrin binding,extracellular matrix (ECM) structural components,ECM receptor interactions,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Macrophages were the predominant infiltrating immune cells in osteosarcoma.Secreted phosphoprotein 1(SPP1),matrix metallopeptidase 2(MMP2),lysyl oxidase(LOX),collagen type V alpha(II)chain(COL5A2),and melanoma cell adhesion molecule(MCAM)presented differential expression between osteosarcoma and normal tissue samples(all P<0.05). Conclusions SPP1,MMP2,LOX,COL5A2,and MCAM are all up-regulated in osteosarcoma,which may serve as potential biomarkers of osteosarcoma.Macrophages are the key infiltrating immune cells in osteosarcoma,which may provide new perspectives for the treatment of osteosarcoma.
Asunto(s)
Neoplasias Óseas , Osteosarcoma , Macrófagos Asociados a Tumores , Neoplasias Óseas/genética , Neoplasias Óseas/inmunología , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Humanos , Osteosarcoma/genética , Osteosarcoma/inmunología , Fosfatidilinositol 3-Quinasas/genética , Macrófagos Asociados a Tumores/inmunologíaRESUMEN
The present study aimed to compare the combined effect of tamoxifen (TAM) and doxorubicin (ADM) with the individual effects of TAM and ADM alone on the MG63 human osteosarcoma cell line. Estrogen receptor (ER) expression was detected in the MG63 cells using reverse transcription PCR. The morphological changes during the inhibition of cell growth were observed using an inverted microscope and a 3-(4, 5-dimethy1-2-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) colorimetric assay following the individual or combined addition of TAM and ADM. ERα and ERß expression was detected in the MG63 cells. The typical apoptotic cell morphology was observed in all groups, with the exception of the control group. The MTT colorimetric analysis demonstrated that the rate of inhibition of cell proliferation in the combination group was significantly increased compared with that in the other groups (P<0.05). ERα and ERß expression was detected in the MG63 human osteosarcoma cells. TAM and ADM alone were able to inhibit cell proliferation. The combination of TAM and ADM significantly enhanced the inhibitory effect, partly through the enhanced sensitivity of the cells to ADM by TAM, which caused the inhibition of cell proliferation and apoptosis.