Objective To screen out key genes associated with osteosarcoma(OS)using bioinformatic methods and find poten-tial diagnostic markers and therapeutic targets for OS.Methods Two OS-related datasets(GSE16088 and GSE42572)were re-trieved and downloaded from the Gene Expression Omnibus(GEO)database,including 21 OS tissue samples and 14 normal bone tis-sue samples.The datasets were corrected to identify differentially expressed genes(DEGs),and the intersecting genes were screened out by the weighted gene co-expression network analysis(WGCNA)and DEGs.The intersecting genes were analyzed by Disease Ontology(DO),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),and protein-protein interaction(PPI)net-work.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic performance of the expressions of the top 10 Hubbe genes of the PPI network for OS,and the OS dataset GSE19276 was used to validate the diagnotic efficacy of the Hub-be genes and screen out the key genes.Subsequently,the correlation of the key genes with infiltrating immune cells was analyzed.The OS tissues and paracancerous tissues of four OS patients surgically treated at the First Affiliated Hospital of Guangxi Universi-ty of Traditional Chinese Medicine from September 1st,2020,to June 30th,2022,were collected,and the expression of the key genes were verified by real-time quantitative polymerase chain reaction(qRT-PCR).Results A total of 687 DEGs including 523 upreg-ulated genes and 164 downregulated genes,2 338 key module genes of WGCNA,and 545 intersecting genes of DEGs and WGCNA key module genes were screened out in the OS and normal bone tissue samples.The DO enrichment analysis showed that the intersecting genes were mainly related to cancers such as urinary system cancer,kidney cancer,germ cell cancer,musculoskeletal system cancer and embryonal cancer.The GO enrichment analysis showed that the intersecting genes were mainly involved in ossification,extracel-lular matrix organization and biomineral tissue development.The KEGG pathway was enriched in the phosphatidylinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway,peroxisome proliferators-activated receptor(PPAR)signaling pathway,and fluid shear stress and atherosclerosis.The Hubbe genes of the top 10 degree in the PPI network analysis were phosphatidylinositol-4,5-bisphos-phate 3-kinase catalytic subunit alpha(PIK3CA),prolyl 4-hydroxylase subunit alpha 1(P4HA1),integrin alpha Ⅴ(ITGAⅤ),histone deacetylase 2(HDAC2),catenin beta 1(CTNNB1),collagen type Ⅲ alpha 1(COL3A1),collagen type Ⅰ alpha 2(COL1A2),transducin beta-like 1X-related protein 1(TBL1XR1),small nuclear ribonucleoprotein polypeptide G(SNRPG),and Ras-related nuclear protein(RAN).The Hubbe genes were validated by plotting ROC curves with the GSE19276 dataset,and the results showed that P4HA1 and ITGAV were more accurate(both AUC>0.8 and P<0.05).The results of qRT-PCR experiments showed that the mRNA expressions of P4HA1 and ITGAV were higher in the OS tissues(both P<0.01).Conclusions P4HA1 and ITGAV may be potential biomarkers and therapeutic targets for OS.
维普
万方数据