Integrated analysis of gene expression and copy number variations in MET proto­oncogene­transformed human primary osteoblasts.

The aim of the present study was to screen the potential osteosarcoma (OS)­associated genes and to obtain additional insight into the pathogenesis of OS. Transcriptional profile (ID: GSE28256) and copy number variations (CNV) profile were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) between MET proto­oncogene­transformed human primary osteoblast (MET­HOB) samples and the control samples were identified using the Linear Models for Microarray Data package. Subsequently, CNV areas and CNVs were identified using cut­off criterion of >30%­overlap within the cases using detect_cnv.pl in PennCNV. Genes shared in DEGs and CNVs were obtained and discussed. Additionally, the Database for Annotation, Visualization and Integrated Discovery was used to identify significant Gene Ontology (GO) functions and pathways in DEGs with P<0.05. A total of 1,601 DEGs were screened out in MET­HOBs and compared with control samples, including 784 upregulated genes, such as E2F transcription factor 1 (E2F1) and 2 (E2F2) and 817 downregulated genes, such as retinoblastoma 1 (RB1) and cyclin D1 (CCND1). DEGs were enriched in 344 GO terms, such as extracellular region part and extracellular matrix and 14 pathways, including pathways in cancer and extracellular matrix­receptor interaction. Additionally, 239 duplications and 439 deletions in 678 genes from 1,313 chromosome regions were detected. A total of 12 genes were identified to be CNV­driven genes, including cadherin 18, laminin subunit α 1, spectrin ß, erythrocytic, ciliary rootlet coiled­coil, rootletin pseudogene 2, ß­1,4-N-acetyl-galactosaminyltransferase 1, G protein regulated inducer of neurite outgrowth 1, EH domain binding protein 1­like 1, growth factor independent 1, cathepsin Z, WNK lysine deficient protein kinase 1, glutathione S­transferase mu 2 and microsomal glutathione S­transferase 1. Therefore, cell cycle­associated genes including E2F1, E2F2, RB1 and CCND1, and cell adhesion­associated genes, such as CDH18 and LAMA1 may be used as diagnosis and/or therapeutic markers for patients with OS.