Bioinformatics Analysis on Key Genes and Immune Infiltration of Osteosarcoma / 中国医学科学院学报

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.

Inhibiting effects of tamoxifen alone and in combination with doxorubicin on the growth of human osteosarcoma cell line MG-63 / 肿瘤

Objective: To compare the effects of combination of TAM (tamoxifen) and ADR (doxorubicin) with the respective effect of TAM or ADR alone on the growth of human osteosarcoma MG-63 cells. Methods: The mRNA expression of ER (estrogen receptor) in MG-63 cells was detected by RT-PCR (reverse transcription-PCR). The morphological changes of MG-63 cells treated with TAM or ADR alone as well as the combination of them were observed under an inverted microscope, and the cell viability was tested by MTT colorimetric assay. Results: The expressions of ERα and ERβ were found in MG-63 cells. The typical apoptotic change of MG-63 cells was observed in each drug intervention group but not occurred in the control group without drug intervention. MTT colorimetric analysis demonstrated that the proliferation inhibition rate of MG-63 cells in the combination group was significantly higher (even two-fold higher) than those in the single-drug groups (with the same dose or double dose) (P < 0.05). Conclusion: ERα and ERβ are expressed in human osteosarcoma MG-63 cells. Both TAM and ADR alone can inhibit the proliferation of MG-63 cells, and the combination of the two can present more obviously inhibitory effect. One of the possible underlying mechanisms might be that TAM can enhance the sensitivity of MG-63 cells to ADR. Copyright © 2013 by TUMOR.